Introduction: The clinical outcomes of direct oral anticoagulant (DOAC) dosage regimens in morbid obesity are uncertain due to limited clinical evidence. This study seeks to bridge this evidence gap by identifying the factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients. Method: A data-driven observational study was carried out using supervised machine learning (ML) models with a dataset extracted from electronic health records and preprocessed. Following 70%:30% partitioning of the overall dataset via stratified sampling, the selected ML classifiers (e.g., random forest, decision trees, bootstrap aggregation) were applied to the training dataset (70%). The outcomes of the models were evaluated against the test dataset (30%). Multivariate regression analysis explored the association between DOAC regimens and clinical outcomes. Results: A sample of 4,275 morbidly obese patients was extracted and analysed. The decision trees, random forest, and bootstrap aggregation classifiers achieved acceptable (excellent) values of precision, recall, and F1 scores in terms of their contribution to clinical outcomes. The length of stay, treatment days, and age were ranked highest for relevance to mortality and stroke. Among DOAC regimens, apixaban 2.5 mg twice daily ranked highest for its association with mortality, increasing the mortality risk by 43% (odds ratio [OR] 1.430, 95% confidence interval [CI] 1.181–1.732, p = 0.001). On the other hand, apixaban 5 mg twice daily reduced the odds of mortality by 25% (OR 0.751, 95% CI 0.632–0.905, p = 0.003) but increased the odds of stroke events. No clinically relevant non-major bleeding events occurred in this group. Conclusion: Data-driven approaches can identify key factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients. This will help design further studies to explore well tolerated and effective DOAC doses for morbidly obese patients.