© 2015, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.This study aimed to compare the outcomes of standard percutaneous nephrolithotomy (PCNL) to PCNL with intraoperative antegrade flexible nephroscopy (IAFN) for treating stones of staghorn nature. We retrospectively analyzed patients treated using PCNL between January 2007 and July 2013. A total of 1250 patients were treated using PCNL, and 166 patients had staghorn stones. All patients had been subjected to a complete blood count, routine biochemical analyses, coagulation tests, a complete urine analysis, and urine cultures. Patients with a positive urine culture had been treated with appropriate antibiotics until the urine culture became negative. After purchasing a flexible renoscope in March 2012, we routinely used this tool to improve the stone-free (SF) rate. The 105 patients who underwent standard PCNL prior to March 2012 were classified as Group 1, and the 61 patients who underwent PCNL + IAFN after that date were classified as Group 2. The two groups had similar and homogeneous demographic data. The fluoroscopy and total operative times were significantly higher in Group 2 than in Group 1 (p < 0.01). Additionally, the hospitalization time (p < 0.01) and the mean hematocrit decrease (p < 0.01) were significantly lower in Group 1. In both groups, the SF rates were higher than 85%, similar to those reported in the literature. Although Group 2 had a slightly better SF rates, this difference was not statistically significant. For staghorn calculi, PCNL combined with IAFN yields excellent outcomes. However, similar prospective studies on larger cohorts should be performed to support our findings.