Objective: In this study, the requirement of analgesia and the analgesic efficacy of a long-acting nonsteroidal antiinflammatory drug (NSAID), piroxicam, were investigated in patients with renal stone disease treated with extracorporeal shock wave lithotripsy (ESWL). Methods: This randomized, placebo-controlled study included 60 patients. Patients were divided into two groups randomly. A single dose of saline (2 ml) was given to the patients in group 1 (n = 20) and 2 ml of 40 mg piroxicam to the patients in group 2 (n = 40). All injections were administered into the gluteal muscle 45 min before ESWL. A verbal rating scale (VRS) was used to evaluate the pain. Groups were compared according to age, sex, weight, height, stone size, number of shock waves, duration of ESWL and VRS scores. Results: There was no statistically significant difference between both groups in demographic data, stone size, number of shock waves and duration of ESWL procedure (p > 0.05). However mean VRS scores were significantly lower in group 2 than in group 1 during and after the ESWL procedure. Conclusion: We considered that analgesic agents should be used to control the pain in second-generation lithotriptors. Piroxicam has clinically significant effects on the pain and also antiinflammatory effects, inhibits ureteric activity, and helps in stone passage.