The aim of this retrospective cohort study was to evaluate independent predictive factors of chronic kidney disease (CKD) in children with severe bilateral primary vesicoureteral reflux (VUR). Between 1970 and 2004, 184 patients were diagnosed with VUR (grades III-V) and were systematically followed up at a single tertiary renal unit. CKD was defined as estimated glomerular filtration rate <75 ml/min per 1.73 m2 body surface area in two consecutive examinations. Risk of CKD was analyzed by the Kaplan-Meier method and Cox's regression model. The probability of CKD for patients with bilateral severe reflux was estimated at 15% by 10 years after VUR diagnosis. After adjustment, four variables remained independently associated with CKD during follow-up: age at diagnosis >24 months [relative risk (RR)=4.8, 95% confidence interval (95%CI), 1.8-12.7, P<0.001], VUR grade V (RR=3.5, 95%CI, 1.5-7.9, P=0.002), bilateral renal damage (RR=2.86, 95%CI, 1.3-6.1, P=0.007), and decade of admission after 1990 as a protective factor (RR=0.16, 95%CI 0.06-0.43, P<0.001). A delay in the diagnosis of VUR more than 12 months after urinary tract infection (UTI) was also a predictive factor in an alternative model (RR=2.2, 95%CI, 1.1-6.6, P=0.03). Prognosis regarding renal function was relatively poor after a long-term follow-up of patients with bilateral severe reflux.