Ibuprofen and acetaminophen are the most commonly used non-opioid analgesics for acute mild-to-moderate pain in pediatric practice and are recommended first-line by major guidelines. Despite frequent use, the comparative analgesic efficacy of these agents specifically in children has remained uncertain because existing evidence often mixes adult and pediatric data and derives from small, heterogeneous trials. This review aimed to restrict synthesis to randomized controlled trials in pediatric populations to clarify comparative effectiveness for acute mild-to-moderate pain.
A systematic literature search was performed through May 2026 across PubMed, Scopus, and Web of Science. The review followed the PRISMA-Children and Adolescents (PRISMA-C) 2026 reporting guideline. Eligible studies were randomized controlled trials comparing ibuprofen with acetaminophen in children and adolescents (aged 0 to <18 years) presenting with acute pain and reporting at least one extractable efficacy outcome.
Continuous outcomes were pooled using standardized mean differences (Hedges' g) with random-effects models; dichotomous outcomes were combined as risk ratios (RRs) with 95% confidence intervals. Risk of bias for individual trials was assessed with the Cochrane RoB 2 tool. Certainty of evidence across outcomes was evaluated using the GRADE framework.
Eight randomized controlled trials enrolling a total of 1325 participants met inclusion criteria for the review. The primary meta-analysis for continuous pain outcomes included data from three pediatric trials with 196 analyzable participants. The pooled standardized mean difference was SMD -0.28 (95% CI -0.57 to 0.00; p = 0.052; I2 = 0%), indicating a small effect size favoring ibuprofen that did not reach conventional statistical significance.
The authors caution that the small number of contributing studies (k = 3) limits the power of I2 to detect heterogeneity and that precision is limited. Thus, while the point estimate favored ibuprofen, statistical evidence for superiority was not established.
For a dichotomous outcome reflecting pain freedom, two trials (n = 114) were pooled and no significant difference was observed between agents (pooled RR 1.03, 95% CI 0.53–1.99; p = 0.93; I2 = 0%).
A prespecified sensitivity analysis that additionally included an adult soft-tissue injury trial reduced the pooled continuous outcome effect toward the null (SMD -0.15, 95% CI -0.38 to 0.09; p = 0.23; I2 = 36.6%), further attenuating evidence of a benefit for ibuprofen when data beyond strictly pediatric trials were considered.
Beyond the trials contributing to pooled estimates, narrative synthesis of the other included studies generally demonstrated comparable analgesic efficacy between ibuprofen and acetaminophen across a range of pediatric acute pain contexts, including postoperative and outpatient settings. The review notes that an analgesic advantage for ibuprofen may be more apparent for pain etiologies with a significant inflammatory component (for example, fracture-related pain), consistent with the anti-inflammatory mechanism of NSAIDs. However, across most acute pediatric pain scenarios, both agents produced clinically meaningful analgesia.
Risk of bias for individual trials was evaluated using Cochrane RoB 2. The overall certainty of evidence for the primary outcomes was rated as low using GRADE. Downgrades were driven chiefly by imprecision (small numbers of events and small sample sizes for pooled outcomes) and indirectness in some studies. The low certainty rating indicates that the true effect may differ substantially from the observed estimates and highlights limitations in the available pediatric-specific randomized trial evidence.
Current randomized trial evidence restricted to pediatric populations does not demonstrate a clear superiority of ibuprofen over acetaminophen for acute mild-to-moderate pain. Both agents appear to provide clinically meaningful analgesia across heterogeneous pediatric pain settings. Clinicians should therefore base the choice between these two first-line non-opioid analgesics on individual patient considerations, including known contraindications to NSAIDs, the likelihood of an inflammatory pain component, age and dosing considerations, and other patient-specific factors.
Given the low certainty of evidence, definitive clinical recommendations favoring one agent over the other cannot be made solely on the basis of the trials included in this review.
The review emphasizes the need for adequately powered, methodologically robust randomized controlled trials conducted specifically in pediatric populations. Key priorities include larger sample sizes to reduce imprecision, standardized and clinically relevant outcome measures, stratification by pain etiology (particularly inflammatory versus non-inflammatory causes), and consistent timing and dosing regimens to reduce heterogeneity. These design improvements are necessary to determine whether a modest superiority of ibuprofen exists for certain pediatric pain types or whether the two agents are effectively equivalent in most acute pediatric contexts.
The review is published in Eur J Pediatr (2026) and reports PMID 42704487 with DOI 10.1007/s00431-026-07383-7. The authors declare no relevant financial or non-financial interests overall, although one author (GPM) received unrestricted grants and participated in an advisory board supported by unrestricted grants; these disclosures are noted in the original article.
Randomized pediatric-specific trial evidence to May 2026 shows a small point estimate favoring ibuprofen for continuous pain reduction (SMD -0.28) that did not meet conventional significance and insufficient evidence of superiority for dichotomous pain freedom. Overall certainty is low, and both ibuprofen and acetaminophen remain reasonable first-line choices for acute mild-to-moderate pediatric pain, with agent selection guided by clinical context and individual patient factors.