OBJECTIVE: To investigate the safety and efficacy of extracorporeal shock wave lithotripsy (ESWL) combined with percutaneous nephrolithotomy (PCNL) for treatment of complex renal calculus. PATIENTS AND METHODS: Seventy-eight patients diagnosed with complex renal calculus and who accepted treatment in our hospital were consecutively selected. Patients were divided randomly into the observation group (n=40) treated by combined ESWL and PCNL and the control group (n=38) treated by PCNL. The effect of treatment between the two groups was compared. RESULTS: The stone-free rate at 3 months after surgery was higher in the observation group than in the control group. There were no differences in the rates of complications (including infection, hemorrhage, collection system perforation and laceration, peripheral organ impairment, and urination extravasation). There were gradual decreases of serum creatinine in the observation group at 4 weeks after extubation of the double J catheter and at 3 months after surgery, while there were no apparent decreases in the control group. The levels of cysteine protease inhibitor and neutrophil gelatinase-associated lipocalin in both groups increased at 4 weeks after extubation of the double J catheter, and decreased at 3 months after surgery. The decreases were more apparent in the observation group compared with the control group, and the differences were statistically significant (p<0.05). CONCLUSIONS: Combined use of ESWL and PCNL to treat complex renal calculus can improve the stone-free rate and renal function, and does not increase the complication rate. It is, therefore, safe and effective.