Pro-inflammatory mediators, including interleukin-6 (IL-6), IL-8, and complement C3a, are released after cardiac surgery as part of the inflammatory response related to blood-biomaterial interaction in the cardiopulmonary bypass circuit. Post operative time course data for these mediators are not fully defined in patients receiving left ventricular assist device (LVAD) support. The authors performed enzyme linked immunosorbent assays for concentrations of IL-6, IL-8, and C3a in plasma in six HeartMate LVAD recipients at the following times: pre operatively; 4, 8, 16, 24, 36, and 48 hr post operatively; daily through the first week; and weekly thereafter for 6 weeks. All patients survived without major complications during the study. Pre operative concentrations of IL-6 and C3a in plasma were significantly increased compared with age matched controls. Post operatively, the concentrations of IL-6 and IL-8 in plasma took longer to return to baseline values after insertion of the LVAD than the trends reported in the literature after routine cardiopulmonary bypass alone. Concentrations of IL-6 and complement C3a continued to decrease to lower than baseline post operatively, reaching statistical significance after 6 weeks of LVAD support. The authors conclude that the presence of the HeartMate LVAD delays the return of pro-inflammatory mediator concentrations back to baseline values compared with routine cardiopulmonary bypass alone, but the device does not appear to be an ongoing source of cytokine release or complement activation.