Objective · To investigate the clinical efficacy of one-stage pyeloplasty and second-stage pyeloplasty after nephrostomy for the treatment of severe hydronephrosis in infants younger than 3 months. Methods · Clinical data of severe hydronephrosis infants younger than 3 months who underwent pyeloplasty at Xinhua Hospital affiliated to the Shanghai Jiao Tong University School of Medicine from Jan. 2012 to Jul. 2015 were retrospectively analyzed. Twenty-five patients received second-stage pyeloplasty after nephrostomy (the A group) and 39 patients received one-stage pyeloplasty (the B group). The operative time, intraoperative blood loss, incidence rate of complications, hospital stay, and postoperative recovery were compared between two groups. Results · Sixty-four severe hydronephrosis infants younger than 3 months were enrolled. The A group has longer operative time and hospital stay and higher incidence rate of postoperative urinary tract infection as compared with the B group [(81 ± 20) min vs (53 ± 18) min, (11.6 ± 2.6) dvs (6.2 ± 1.5) d, and 36.0% vs 17.9%), respectively]. The hydronephrosis and renal function in two groups were significantly improved 6 months after surgery and the difference between two groups was not statistically significant. Conclusion · Second-stage pyeloplasty after nephrostomy has no obvious advantage for the treatment of severe hydronephrosis in infants younger than 3 months with respect to the final morphology and function recovery of involved kidneys. One-stage pyeloplasty is safe and effective and should be served as the preferred method for the treatment of severe hydronephrosis in infants.