ObjectiveTo validate the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN) clinical prediction rule on an independent cohort of infants with fever without a source (FWS).DesignSecondary analysis of a prospective registry.SettingPaediatric emergency department of a tertiary teaching hospital.PatientsInfants ≤60 days old with FWS between 2007 and 2018.Main outcome measuresPrevalence of serious bacterial infection (SBI) and invasive bacterial infection (IBI) in low-risk infants according to the PECARN rule.ResultsAmong the 1247 infants included, 256 were diagnosed with an SBI (20.5%), including 38 IBIs (3.1%). Overall, 576 infants (46.0%; 95% CI 43.4% to 49.0%) would have been classified as low risk of SBI by the PECARN rule. Of them, 26 had an SBI (4.5%), including 5 with an IBI (2 (0.8%) diagnosed with bacterial meningitis). Sensitivity and specificity of the PECARN rule were 89.8% (95% CI 85.5% to 93.0%) and 55.5% (95% CI 52.4% to 58.6%) for SBI, with an area under the curve of 0.726 (95% CI 0.702 to 0.750). Its sensitivity to identify SBIs was 88.6% (95% CI 82.0% to 92.9%) among infants with a <6-hour history of fever (54.9% of the infants included).ConclusionsThe PECARN clinical rule for identifying SBI performed less well in our population than in the original study. This clinical rule should be applied cautiously in young infants with a short history of fever.