Introduction: The Medication Regimen Complexity -Intensive Care Unit (MRC-ICU) is the first tool for measuring medication regimen complexity in critically ill patients. This study tested machine learning (ML) models to investigate the relationship between medication regimen complexity and patient outcomes. Methods: This study was a single-center, retrospective observational evaluation of 130 adults admitted to the medical ICU. The MRC-ICU score was utilized to improve the inpatient model’s prediction accuracy. Three models were proposed: model I, demographic data without medication data; model II, demographic data and medication regimen complexity variables; and model III: demographic data and the MRC-ICU score. A total of 6 ML classifiers was developed: k-nearest neighbor (KNN), naïve Bayes (NB), random forest, support vector machine, neural network, and logistic classifier (LC). They were developed and tested using electronic health record data to predict inpatient mortality. Results: The results demonstrated that adding medication regimen complexity variables (model II) and the MRC-ICU score (model III) improved inpatient mortality prediction.. The LC outperformed the other classifiers (KNN and NB), with an overall accuracy of 83%, sensitivity (Se) of 87%, specificity of 67%, positive predictive value of 93%, and negative predictive value of 46%. The APACHE III score and the MRC-ICU score at the 24-hour interval were the 2 most important variables. Conclusion and Relevance: Inclusion of the MRC-ICU score improved the prediction of patient outcomes on the previously established APACHE III score. This novel, proof-of-concept methodology shows promise for future application of the MRC-ICU scoring tool for patient outcome predictions.