OBJECTIVE: This study aims to evaluate the prevalence, clinical characteristics, severity, mortality, and outcomes of COVID-19 infection in heart transplant recipients, focusing on risk factors for severe disease. METHODS: A retrospective, observational study was conducted on adult heart transplant patients (HTxs) at Fuwai Hospital from December 1, 2022, to February 28, 2023, with follow-up until May 30, 2024. Clinical data were collected via telephone surveys and medical records. Logistic regression analyses were conducted to explore risk factors for severe disease. RESULTS: In total, 728 of the 916 HTxs were infected with COVID-19 (79.48%); the vaccination rate was 27.95%. Of infected cases, 56.18% were mild, 18.82% moderate, 19.26% severe, and 5.77% critical. Severe disease occurred in 25.00%, with a mortality rate of 4.54%. Logistic regression analyses revealed that age (OR 1.048, 95% CI 1.031-1.066, P<0.001), history of diabetes (OR 1.829, 95% CI 1.221-2.740, P=0.005), Chronic kidney disease stage≥3 (OR 2.557, 95% CI 1.650-3.963, P<0.001) and immunosuppressive regimens including sirolimus (OR 1.639, 95% CI 1.145-2.348, P=0.007) were independent risk factors for severe infection, while age (OR 1.102, 95% CI 1.053-1.154, P<0.001) and Chronic kidney disease stage≥3 (OR 6.342, 95% CI 2.980-13.499, P<0.001) were independent risk factors for post-infection mortality. COVID-19 vaccination (OR 0.169, 95% CI 0.039-0.733, P=0.018) was found to be a protective factor against post-infection mortality. CONCLUSION: COVID-19 vaccination is recommended for HTxs to reduce severe outcomes and mortality. Sirolimus use was independently associated with severe infection, highlighting the need for careful management of immunosuppression.