Objective: To study the influence of a novel intermittent sequential pneumatic compression device (Lympha-press) on the adverse cardiac and peripheral hemodynamic changes induced by positive-pressure pneumoperitoneum (PPPn) in laparoscopic surgery. Summary Background Data: Creation of PPPn is known to cause adverse central and peripheral hemodynamic changes. An intrasubject observational study was undertaken to quantitate these adverse changes and to assess the influence of an intermittent sequential pneumatic compression system on these adverse hemodynamic changes during laparoscopic surgery with PPPn. Methods: The study involved 16 consecutive patients undergoing laparoscopic surgery with PPPn of 12 mmHg and 30° head-up tilt position. The following peripheral hemodynamic recordings were made using Doppler ultrasound: peak systolic velocity (PSV), end diastolic velocity (EDV), and cross-sectional area of the femoral vein. Central monitoring included cardiac output and stroke volume by transesophageal Doppler, blood pressure, and pulse. The hemodynamic state based on these parameters was assessed before induction of PPPn with the anesthetized patient in the supine position, after induction of PPPn and head-up tilt position with Lympha-press off, and during PPPn and head-up tilt position with Lympha-press on, and after desufflation with the patient in the supine position under general anesthesia. Results: Positive-pressure pneumoperitoneum and the head-up tilt position resulted in a 33% reduction in PSV, a 21% reduction in EDV, and a 29% increase in cross-sectional area of the femoral vein. This was associated with a 20% reduction in cardiac output and an 18% reduction in stroke volume. Activation of Lympha-press during PPPn and the head-up tilt position resulted in a 129% increase in PSV and a 55% increase in EDV by 55%. It also increased the cardiac output by 27% and stroke volume by 16%, with no effect on cross-sectional area. Compared with the pre-PPPn stage, there was no difference in cardiac output or stroke volume, but the PSV was higher by 78% and the EDV by 32%. After abdominal desufflation in the supine position, the cardiac output and stroke volume were restored to the pre-PPPn level, but persistent and significant elevations were observed during the period of study in PSV, EDV, and cross-sectional area. Conclusions: Significant and individually variable central and peripheral hemodynamic changes are encountered during laparoscopic surgery with PPPn and the head-up tilt position. These are reversed by intermittent sequential pneumatic compression using Lympha-press.