Renal cysts are common in the adult population. Symptomatic cysts traditionally have been treated by percutaneous aspiration with injection of sclerosant agents. Our aim was to compare the efficacy and side effects of ethanol and sodium tetradecyl sulfate (STDS) as sclerosants for symptomatic simple renal cyst.Sixty-five patients with 68 symptomatic simple renal cysts were included in this study. An 8F pigtail catheter was inserted into the cyst under ultrasound guidance followed by aspiration of the cyst fluid. Either 95% ethanol (N = 34) or 3% STDS (N = 34), assigned randomly, was then instilled into the empty sac. Patients recorded any flank pain on a visual analog scale and were followed up by ultrasonography for 6 to 18 months.There was complete ablation of 28 (82%) and 26 (76%) cysts, partial regression of 3 (9%) and 6 (18%) cysts, and failure of treatment in 3 (9%) and 2 (6%) cysts in the ethanol and STDS groups, respectively. There was no major complication in either group. The pain caused by the injection was significantly less for the group receiving STDS (pain score 2.1 +/- 1.1 v 3.8 +/- 1.2 for ethanol; P = 0.019).Ethanol and STDS are simple, noninvasive, cost-effective, and well-tolerated sclerosants for the treatment of simple renal cysts. We prefer STDS as a first choice because it causes less pain.