BACKGROUND: Transfusion of platelets is common in cardiac surgery, and while there are guidelines for their use, there are concerns about potential risks. We aimed to assess the impact of platelet transfusion on mortality, thrombosis, and infection in this patient group. STUDY DESIGN AND METHODS: A retrospective cohort study of all patients at St Vincent's Hospital Melbourne who underwent a first cardiac surgery procedure from June 2001 to June 2014 was conducted. A propensity-weighted analysis was performed to examine the association between intraoperative platelet transfusion and outcomes. RESULTS: A total of 5233 patients met inclusion criteria, and 531 (10.15%) received intraoperative platelet transfusion (median two platelet doses, interquartile range, 1-17). Patients receiving platelets were older, had higher body mass index, lower rates of diabetes and dyslipidemia, higher rates of infective endocarditis, recent myocardial infarction and unstable angina, and exposure to aspirin or clopidogrel. On univariable analysis, platelet transfusion was associated with increased 30-day mortality (2.4% vs. 10.55%, p<0.001), return to theatre for bleeding (3.23% vs. 13.37%, p<0.001), and rates of any infection (9.26% vs. 19.17%, p<0.001). After adjusting for confounders, platelet transfusion was not associated with increased risk of 30-day mortality or infective complications. Platelet transfusion was associated with higher rates of return to theatre (relative risk [RR], 2.46; confidence interval [CI], 1.42, 4.04; p=0.001) and decreased risk of thromboembolic events (RR, 0.28; CI, 0.15, 0.51; p<0.001). CONCLUSION: Platelet transfusion was not associated with increased mortality or infective complications following first cardiac surgery. Further prospective studies are required to identify patients most likely to benefit from platelet transfusion.