Background: This study investigates the use of modern machine learning (ML) techniques to improve prediction of survival after orthotopic heart transplantation (OHT). Methods: Retrospective study of adult patients undergoing primary, isolated OHT between 2000-2019 as identified in the United Network for Organ Sharing (UNOS) registry. The primary outcome was one-year post-transplant survival. Patients were randomly divided into training (80%) and validation (20%) sets. Dimensionality reduction and data re-sampling were employed during training. Multiple machine learning algorithms were combined into a final ensemble ML model. Discriminatory capability was assessed using area under receiver-operating-characteristic curve (AUROC), net reclassification index (NRI), and decision curve analysis (DCA). Results: A total of 33,657 OHT patients were evaluated. One-year mortality was 11% (n=3,738). In the validation cohort, the AUROC of singular logistic regression was 0.649 (95% CI 0.628-0.670) compared to 0.691 (95% CI 0.671-0.711) with random forest, 0.691 (95% CI 0.671-0.712) with deep neural network, and 0.653 (95% CI 0.632-0.674) with Adaboost. A final ensemble ML model was created that demonstrated the greatest improvement in AUROC: 0.764 (95% CI 0.745-0.782) (p<0.001). The ensemble ML model improved predictive performance by 72.9% ±3.8% (p<0.001) as assessed by NRI compared to logistic regression. DCA showed the final ensemble method improved risk prediction across the entire spectrum of predicted risk as compared to all other models (p<0.001). Conclusions: Modern ML techniques can improve risk prediction in OHT compared to traditional approaches. This may have important implications in patient selection, programmatic evaluation, allocation policy, and patient counseling and prognostication.