The purpose of this study was to report the clinical course of medium-long-term follow-up of children with prenatally detected vesicoureteral reflux (VUR). Between 1986 and 2004, 53 (41 males) children with VUR detected by investigation of prenatal hydronephrosis were followed up for a mean time of 66 months (range: 6-200 months). Newborns were investigated by ultrasound, voiding cystourethrogram (VCUG) and DMSA scan. Follow-up clinical visits were performed at 6-month intervals. After 24 months patients were investigated by conventional VCUG or direct isotope cystogram. Survival analysis was performed in order to evaluate the resolution of the reflux. Differences between subgroups (mild vs moderate/severe reflux) were assessed by the two-sided log rank test. Thirty (58%) infants presented bilateral VUR, for a total of 83 renal units. There was a predominance of severe reflux (54%). Renal damage was detected in 33.7% of the units on first renal scan. There was a significant correlation between severe reflux and renal damage scars (RR=3.4, 95% confidence interval [CI], 1.4-8, p=0.002). Forty-seven patients were treated with continuous prophylaxis. One patient developed systolic hypertension. Urinary tract infection occurred in 12 (25%) children conservatively managed. VUR resolution was evaluated in 56 renal units. Spontaneous resolution was observed in 25 units (45%). At 48 months after diagnosis, 75% of the cases of mild reflux (I-III) and 37% of severe reflux (IV-V) had resolved (log-rank, 5.6, p=0.017). There was an improvement of nutritional parameters between admission and the end of follow-up. In conclusion, the clinical course of prenatally detected VUR followed up on a medium-long-term basis is relatively benign. Our study corroborates the results obtained in other series of infants with reflux that emphasized the heterogeneity of this disorder.