Objective To systematically review the effectiveness and safety of flexible ureteroscope lithtripsy (fURL) and percutaneous nephrolithotomy (PCNL) in treating renal calculus. Methods Such databases as MEDLINE, EMbase, The Cochrane Library, CNKI, CBM, VIP, and WanFang Data from January, 1990 to August, 2012 were searched to comprehensively collect the clinical trials that compared fURL and PCNL in treating renal calculus. Two reviewers independently screened studies according to exclusion and inclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.1 software. Results Eight non-randomized controlled trials involving 536 patients were included. The results of meta-analysis showed that, PCNL was better than fURL in stone clearance (OR=0.26, 95%CI 0.15 to 0.46), but fURL was better than PCNL in postoperative pyrexia (OR=0.1, 95%CI 0.42 to 3.35), the incidence of blood transfusion (OR=0.17, 95%CI 0.03 to 1.00), and the duration of hospitalization (P=0.45, I2=0%). Conclusion Current evidence has proved that PCNL is better than fURL in decreasing stone clearance, fURL is better than PCNL in complication, the duration of hospitalization, and medical costs.