Patients who received a total artificial heart (TAH) at Virginia Commonwealth University (VCU) between January 1, 2010 and December 31, 2011 were identified from the VCU Mechanical Circulatory Support Clinical Database. Retrospective data extraction from the medical records was performed from the time of TAH implantation until heart transplantation or death. Infections were classified as confirmed or suspected. Twenty-seven men and five women, mean age 49.5 years (range 24–68 years) received a TAH. The mean duration of TAH support was 225 days (range 1–1,334 days). Of the 32 patients, 4 (12.5%) died and 28 (87.5 %) underwent heart transplantation. Causes of death were pneumonia (n = 1), TAH malfunction (n = 1), refractory cardiogenic shock (n = 1), and respiratory failure (n = 1). Seventy documented and 13 suspected infections developed in 25 patients (78%). The most common sources of infection were urinary tract (n = 26), respiratory tract (n = 18), and bloodstream (n = 11). There were five pump infections and two driveline infections. The number of infections per patient ranged from 0 to 10. Sixteen different pathogens were identified; the most common were: Klebsiella pneumoniae (n = 15), coagulase-negative Staphylococci (n = 10), Enterococcus species (n = 9), and Enterobacter species (n = 8). Mortality directly attributable to infection was infrequent.