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Background and objectives: Machine learning approaches using random forest have been effectively used to provide decision support in health and medical informatics. This is especially true when predicting variables associated with Medicare reimbursements. However, more work is needed to analyze and predict data associated with reimbursements through Medicare and Medicaid services for physical therapy practices in the United States. The key objective of this study is to analyze different machine learning models to predict key variables associated with Medicare standardized payments for physical therapy practices in the United States. Materials and Methods: This study employs five methods, namely, multiple linear regression, decision tree regression, random forest regression, K-nearest neighbors, and linear generalized additive model, (GAM) to predict key variables associated with Medicare payments for physical therapy practices in the United States. Results: The study described in this article adds to the body of knowledge on the effective use of random forest regression and linear generalized additive model in predicting Medicare Standardized payment. It turns out that random forest regression may have any edge over other methods employed for this purpose. Conclusions: The study provides a useful insight into comparing the performance of the aforementioned methods, while identifying a few intricate details associated with predicting Medicare costs while also ascertaining that linear generalized additive model and random forest regression as the most suitable machine learning models for predicting key variables associated with standardized Medicare payments. [ABSTRACT FROM AUTHOR]