PURPOSE: Urinary tract infection is common in children and may be associated with significant urinary tract pathology. Many children are investigated for vesicoureteral reflux after the first urinary tract infection but less than a quarter have reflux. Imaging with voiding cystourethrogram is not without risk. An approach was proposed to predict reflux in children with a urinary tract infection. We sought to validate a preestablished clinical decision rule to target voiding cystourethrogram more efficiently in children after the first urinary tract infection. MATERIALS AND METHODS: We tested the usefulness of a clinical decision rule to predict vesicoureteral reflux in 406 consecutive children younger than 5 years who were treated or referred for consultation due to an acute urinary tract infection. Symptoms and signs of urinary tract infection and imaging findings were analyzed. RESULTS: Vesicoureteral reflux was found in 120 children (35%), including 69 (20%) with grade III-V reflux. An abnormal ultrasound finding was seen in 71 cases (18%) but was not associated with reflux. The clinical decision rule appeared to have poor sensitivity of only 24% to identify grade III-V reflux. We found it impractical to predict vesicoureteral reflux in children with a urinary tract infection. CONCLUSIONS: Results show that it is not possible to predict grade III-V vesicoureteral reflux reliably using the clinical decision rule. The recent guidelines recommending a search for reflux after a urinary tract infection in children cannot be revised using this decision rule.