Objectives:The risk of developing venous thromboembolism (VTE) in urologic patients undergoing major surgery without thromboprophylaxis is high (up to 40%). The aims were to study the acceptability rate of and overall patient satisfaction with an automatic sequential leg compression system and the short-term effectiveness of a combined VTE prevention modality. Methods: One-hundred and eighty-four consecutive patients undergoing radical retropubic prostatectomy were postoperatively treated with enoxaparine and intermittent pneumatic compression of the thigh. By completing a questionnaire, the patients were prospectively studied to evaluate the comfort and tolerability of a compression device (SCD Response Compression System; Covidien, Gosport, UK). The patients were monitored for complications and development of VTE for up to 4 weeks postoperatively. The device used ensures customized and effective compression therapy matching the patient’s individual vascular refill by sequential, gradient, circumferential microprocessor-controlled compression cycles. Results: No clinically evident VTE, critical bleeding or postoperative death occurred during the study period. Drain output was associated with transfusion requirement (p < 0.001), obesity (p < 0.02) and longer operation duration (p < 0.001). The sequential compression devices were well tolerated by 63% of the patients, in that the sleeves were judged as being pleasant (72%) and nonoppressive (79%). Patients reported bothersome insomnia (23%) and noise (44%), and early removal was required in 3%. Conclusions: Combined mechanical and pharmacological thromboprophylaxis was highly effective, well tolerated, and safe. The device tested showed a high comfort and tolerability profile. The use of combined modalities for VTE prophylaxis is justified in patients at very high risk of VTE, such as those undergoing radical retropubic prostatectomy.