OBJECTIVE To evaluate the efficacy of single-session percutaneous sclerotherapy with needle aspiration or catheter drainage, under ultrasound (US) or computed tomography (CT) guidance, based on cyst size and depth in 22 symptomatic simple renal cysts. METHODS Sclerotherapy with 95% alcohol for 20 min was performed in 22 symptomatic simple renal cysts in 15 patients. The method (aspiration or drainage) was chosen according to cyst size and depth: catheter drainage was done for larger (>6 cm) and shallow (<7.5 cm) cysts (N=12) and needle aspiration was done for smaller (<6 cm) or deeper (>7.5 cm) cysts (N=10). The median follow-up period was 6.0 months (range 1-62). RESULTS Volume reduction of cysts (mean and median, respectively) was 94.1% and 97.0%. Average cyst volume reduction (mean and median, respectively) was 94.7% and 96.0% with US-guided methods and 93.3% and 99.0% with CT-guided methods (P=0.382). Median volume loss was 97.5% with needle aspiration and 96.5% with catheter drainage (P=0.839). No correlation between the groups and volume reduction was found. All procedures were successful. No major complications or recurrences were noted. CONCLUSIONS Single-session percutaneous alcohol sclerotherapy with needle aspiration or catheter drainage, under US or CT guidance, is an effective and safe method for treating symptomatic simple renal cysts. CT-guided needle aspiration may be more suitable for treating deeper and/or smaller (<6 cm) cysts, while US-guided catheter drainage may be preferable in cases of shallow and/or larger (>6 cm) cysts.