To evaluate whether prolonged catheter drainage with negative pressure yields better results than single-session alcohol sclerotherapy in the treatment of symptomatic non-parasitic benign liver cysts. Forty patients were randomly assigned to two groups in a 24-month prospective controlled trial. One group was treated with ultrasound-guided prolonged catheter drainage with negative pressure (20 patients with 24 cysts) and the other group with single-session alcohol sclerotherapy (20 patients with 23 cysts). Patient demographics, clinical characteristics, treatment outcome, and complications were analyzed. The median volumes and 95% CI (confidence interval) for the medians and interquartile ranges of all 47 cysts before treatment and on last follow-up were: 389 ml, 143-1,127 ml, 136-1,300 ml, and 0 ml, 0-10 ml, and 0-23 ml, respectively (P<0.0001). The average volume reduction was 92.4% (range, 74.9-100%), 94.2 % (range, 74.9-100%) in the drainage and 90.2% (range, 76.9-100%) in the sclerotherapy group. Twenty-seven cysts (57.4%) disappeared completely, 16 (66.7%) in the drainage and 11 (47.8%) in the sclerotherapy group. No differences in average volume reduction, final volume and disappearance of the cysts between the groups were noted. The hospital stay was 1 day for all patients. Percutaneous treatment is safe and effective for hepatic non-parasitic cysts. Prolonged catheter drainage with negative pressure and single-session alcohol sclerotherapy had similar results.