Objectives: To compare the outcome of laparoscopic pyelolithotomy (LP) using the transperitoneal and the retroperitoneal routes. Methods: Demographics, intraoperative and postoperative clinical parameterswere evaluated in 48 laparoscopic pyelolithotomies performed in patients with renal pelvic calculi of diameter >30 mm. The differences between the transperitoneal and retroperitoneal routes were analyzed. Results: Twenty-seven LP were performed using the transperitoneal approach (TLP), and 21 using the retroperitoneal approach (RLP). Apart from weight, the patients’ demographics and stone size were similar in the two groups. Between the RLP and the TLP routes, the operative time was 112.1 versus 93.2 min (P = 0.01), mean time for oral intake was 1.9 versus 1.2 days (P < 0.01), and mean hospital stay was 5.2 versus 3.8 days (P < 0.01). The mean postoperative analgesic requirement (2.4 vs 2.2 days, P = 0.41), mean convalescence days (9.7 vs 10 days, P = 0.56), and mean estimated blood loss (57.2 vs 62.9 ml, P = 0.5) were similar between RPL and TPL respectively. The stone-free rate at 3 months follow-up was comparable (88.9% vs 90.5%, P = 0.86). The postoperative complications were not significantly different. Conclusions: Compared with the TLP approach, RLP for large renal pelvic stone resulted in a shorter operative time, a shorter resumption time for normal oral intake, and a shorter hospital stay. As the other clinical outcomes are similar, including the stone-free rate, we recommend the RLP route for LP.