Objective: INTERMACS is a registry of mechanical circulatory support devices sponsored by the National Institutes of Health. This analysis uses INTERMACS data to define the time course, incidence, and outcome of infection adverse events focusing on the first 3 months after implant. Methods: Patients entered into INTERMACS from June 23, 2006, to September 30, 2008, were analyzed. Preimplant data (demographics, hemodynamics, and laboratory values), infection adverse events, and other outcomes were recorded. Infection adverse events were analyzed to compare infection rates in subgroups of patients and define risk factors for death. Results: The analysis was confined to pulsatile mechanical circulatory support devices. A total of 593 patients from 88 institutions were entered. Infection was a relatively common event within the first 3 months of implant and was significantly (P = .005) more common in patients with biventricular assist devices than in patients with left ventricular assist devices, although the prevalence of infection equalized in months 4 to 12. Infection had a significant adverse effect on survival. Independent risk factors for death included support with a biventricular assist device, older age, severity of patient illness implantation of the device (INTERMACS level 1), and higher blood urea nitrogen. Conclusions: Infection remains a relatively frequent adverse event and is associated with decreased survival. Interventions to prevent infection that focus on the preoperative and immediate postoperative periods are the ones most likely to achieve success by diminishing the incidence of infection during the initial 3 months after implantation. Rotary (continuous-flow) pumps are expected to have lower infection rates, but this remains to be seen.