BACKGROUND: Research indicates that gender mismatch of organ donor and recipient may adversely affect outcomes in heart transplant (HT) patients. However, there is a paucity of literature on gender-mismatched outcomes in patients receiving an HT, and only a few outcomes have been investigated. OBJECTIVES: Objectives were to (1) determine if gender-mismatched HT recipients experienced decreased survival, more posttransplantation complications, and more days of hospitalization during the first postoperative year as compared with gender-matched recipients and (2) identify risk factors for decreased survival. METHODS: Patients were 347 HT recipients; 21.3% (74) received a heart from the opposite gender. Three groups were compared: group 1: same gender donor-recipient (273 [78.7%]: 36 women, 237 men); group 2: female donor-male recipient (40 [11.5%]); group 3: male donor-female recipient (34 [9.8%]). Ten outcomes were compared with Kaplan-Meier survival analysis, logistic regression, and multivariate analysis of covariance, using a Bonferroni-adjusted P ≤ .005. Risk factors for decreased survival were examined with Cox regression. RESULTS: Gender-mismatched HT patients with a male donor and a female recipient (group 3) had more treated acute rejections and were rehospitalized for more days after HT discharge during the first postoperative year as compared with gender-matched patients. No significant differences were found in 8 other first-year outcomes: number of deaths, survival time, hospital length of stay for HT surgery, cardiac allograft vasculopathy, severe renal dysfunction, new-onset steroid-induced diabetes, nonskin cancers, or the number of infections treated with an intravenous antibiotic. Risk factors for decreased year 1 survival were higher year 1 cholesterol, earlier intravenous-treated infection, severe renal dysfunction, earlier treated rejection, and diabetes (both preexisting and new-onset steroid-induced diabetes). CONCLUSION: Gender-mismatched HT recipients had more complications due to rejection and higher resource utilization due to more rehospitalization during the first postoperative year as compared with gender-matched recipients. Therefore, these problem areas may provide targets for possible interventions. Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.