The interaction of circulating monocytes and platelets may contribute to thrombosis and inflammation in heart failure. We studied platelet and monocyte activation in 15 patients with end-stage heart failure who underwent left ventricular assist device (LVAD) placement. Blood samples were collected before and at 3, 7, 14, 21, 30, 60, 90, and 180 days after LVAD implantation. We used flow cytometry to measure the expression of platelet surface glycoprotein receptors, platelet activation markers, monocyte markers, the formation of platelet complexes with monocytes (MPC), granulocytes, and lymphocytes, and platelet glycoprotein (GP) IIIa (PLA1/A2) polymorphism. The average preoperative percentage of CD62P-positive platelets was 27% +/- 17%; CD63-positive platelets, 9.7% +/- 8.1%; thrombospondin-positive platelets, 9.9% +/- 6.8%; and MPCs, 10.3% +/- 4.3%. No significant changes were noted in the percent of activated platelets with the three markers. Percentage of MPCs increased over time and peaked at day 21 (26.3% +/- 10.6%, p = 0.0028). In about 40% of patients, activation markers remained high up to 60 days after implantation. We found a significant positive correlation between MPC and CD14 (R = 0.60, p = 0.011), and a negative correlation between MPC and P-selectin glycoprotein ligand-1 (PSGL-1) (R = -0.84, p < 0.0001), and between CD14 and PSGL-1 (R = -0.46, p = 0.022) indicating monocyte activation. These results indicate increased platelet and monocyte activation and interactions in patients undergoing long-term LVAD support.