Purpose: We evaluated the relationship between bladder urine transforming growth factor-beta 1 concentration and severity of hydronephrosis in newborns with unilateral prenatal hydronephrosis. Materials and Methods: We prospectively studied all newborns presenting with unilateral prenatal hydronephrosis between January 2005 and 2007. Patients with associated anomalies, vesicoureteral reflux, contralateral pathology or ipsilateral ureteral dilatation were excluded from study. Postnatal evaluation included voiding cystourethrography, renal ultrasonography and determination of bladder urine transforming growth factor-beta 1 concentration. Diuretic renal scans were performed in patients with initial grade 3 or 4 hydronephrosis or increasing hydronephrosis during followup. Pyeloplasty was performed when a well tempered renogram showed an obstructive drainage curve with a half-time greater than 20 minutes and/or an obstructive washout curve pattern during the diuretic phase. Patients were analyzed in observational and surgical groups. We studied the longitudinal changes in bladder urine transforming growth factor-beta 1 in each group and compared concentration levels in the first 3 months of life in both groups. Results: A total of 42 newborns were included. The observational group consisted of 31 patients followed for a mean of 14 +/- 6 months. During the first 3 months, from 3 to 12 months and in the second year of life mean ultrasound grade and bladder urine transforming growth factor-beta 1 decreased from 2.3 to 1.7 to 1.2 (p <0.05) and from 11.5 to 8.6 to 6.1 pg/mmol creatinine (p <0.05), respectively. Pyeloplasty was performed in 11 patients at a mean age of 6 +/- 5 months. Mean followup was 7 +/- 5 months. In the first 3 months, preoperatively and at 3 to 12 months postoperatively mean ultrasound grade and bladder urine transforming growth factor-beta 1 were 3.5, 4 and 3 (p >0.05), and 23, 29 (p >0.05) and 8 pg/mmol creatinine (p <0.003), respectively. Mean bladder urine transforming growth factor-beta 1 levels in the first 3 months of life were 23 +/- 14 and 11.5 +/- 8 pg/mmol. creatinine in the surgical and observational groups, respectively (p <0.001). Limiting comparison to the 23 patients with initial grades 3 and 4 hydronephrosis revealed levels of 23 +/- 14 and 13 +/- 9 pg/mmol. creatinine in the surgical and observational groups, respectively (p <0.02). At a cutoff of 17 pg/mmol creatinine bladder urine transforming growth factor-beta 1 in the first 3 months of life was 82% sensitive and 86% specific in predicting surgery. Conclusions: Bladder urine transforming growth factor-beta 1 changes through time are associated with similar changes in hydronephrosis grade. Bladder urine transforming growth factor-beta 1 in the first 3 months of life can predict the need for surgery in newborns with prenatal hydronephrosis.