The prevalence, natural history, and implications of reactive thrombocytosis after liver transplantation (LT) are unknown. Prospectively collected data from July 2000 to February 2006 were analyzed. Post–LT thrombocytosis was defined as a platelet count of >450 × 103/μL lasting for >7 days and starting within 8 weeks of transplantation. In patients who survived >8 weeks, graft and patient outcomes were compared with liver transplant recipients who survived >8 weeks and did not develop any thrombocytosis. Post-LT thrombocytosis was seen in 92 (14.7%) of 627 patients. The median onset was on day 13 (range, days 1-44) and the peak platelet count was seen on day 17 (range, days 3-110). The median duration of thrombocytosis was 25 days (range, 7-1,253 days), with a median peak platelet count of 625 × 10/μL (range, 472-1,381 × 10/μL). Seronegative fulminant hepatic failure was the indication for transplantation in 18% of patients with post-LT thrombocytosis compared with 3% of controls (P < 0.001). There was a lower proportion of patients transplanted for hepatitis C–related cirrhosis in the thrombocytosis group (10% vs. 18%, P = 0.04). The occurrence of hepatic arterial thrombosis was similar in the 2 groups (5% vs. 4%, P = NS). None of the 4 patients with platelet count higher than 1,000 × 10/μL developed thrombotic complications. Post-LT thrombocytosis is more often associated with seronegative fulminant hepatic failure, and there is a negative association with hepatitis C–related cirrhosis. Post-LT thrombocytosis does not increase the risk of hepatic artery thrombosis, and patients without thrombotic complications should not be treated. Liver Transpt 13: 1598–1602. 2007. © 2007 AASLD.