OBJECTIVE Our purpose was to evaluate the safety and therapeutic efficacy of single-session prolonged alcohol sclerotherapy in treating large hepatic cysts. A therapeutic comparison between 4-hour and 2-hour retention techniques was also studied. METHODS Twenty-seven patients with 31 hepatic cysts were enrolled in this study. Seventeen patients (18 cysts) were treated by alcohol retention for 4 hours (group 1) and 10 patients (13 cysts) for 2 hours (group 2). The mean diameter of the hepatic cysts was 12.4 cm (range, 8-23 cm) with a comparable size range in each group. The sclerosing agent used was 95% alcohol, and the maximum amount was limited to 200 mL. Patients changed position and vital signs were monitored every 10-15 minutes. The blood alcohol concentrations were checked hourly for 5 consecutive hours in the initial nine patients. The nonparametric Mann-Whitney U test was used to compare the difference in characteristics and treatment results of the subjects between these two groups. The level of statistical significance was set at a p value of less than 0.05. RESULTS All but one patient in group 2 tolerated the entire course of sclerotherapy. The mean aspirated volume and mean injected alcohol volume of the hepatic cysts were 730 mL and 138.3 mL, respectively, in group 1 patients, and 931 mL and 139 mL, respectively, in group 2 patients. The mean maximum blood alcohol concentration was 128.2 mg/dL (range, 60-199 mg/dL) at 3-4 hours after alcohol instillation. The mean posttherapy residual cystic diameter was 2.5 cm (range, 0-6 cm), with an average volume reduction rate of 98.3% and 97.7%, respectively, for patients in group 1 and group 2 after a mean follow-up period of 29.6 months (9-59 months). No statistical differences of the mean reduction rate between the two groups were noted. CONCLUSIONS Long retention of the alcohol in a single-injection technique is safe and effective. Two-hour alcohol retention has a comparable efficacy to that of 4-hour retention.