Abstract Objective: During a pneumoperitoneum intraoperative intermittent sequential pneumatic compression (ISC) neutralizes venous stasis in the lower extremities and may also have an influence on systemic fibrinolytic activity. Design: Controlled study to evaluate whether ISC stimulates intravascular fibrinolytic activity. Setting: University-Hospital. Materials: 26 patients underwent laparoscopic cholecystectomy with (+ISC, n = 10) or without (–ISC, n = 16) ISC. Intervention: Intraoperative intermittent sequential compression of the lower extremities. Main outcome measures: Major endpoint – postoperative plasma activity of tissue-plasminogen-activator (t-PA). Minor endpoints – postoperative plasminogen-activator-inhibitor-1 (PAl-1) activity, plasmin-antiplasmin-complex (PAP) concentration, concentration of total fibrin degradation products (TDP), and D-Dimer concentration. Results: There was no difference in age, sex, body mass index (BMI), and properative fibrinolytic activity between the groups. Postoperative t-PA-activity (P =0.3), PAI-1-activity (P =0.9), PAP- (P =0.5), TDP-(P =0.2), and D-Dimer-concentrations (P =0.1) were also not different between both groups. Conclusion: During laparoscopic cholecystectomy intraoperative ISC does not activate systemic intravascular fibrinolysis. Because of the positive hemodynamic effect of ISC during pneumoperitoneum, studies of the antithrombotic efficacy of this tool are needed in the setting of laparoscopic surgery.