The present study sought to investigate the risk factors for physical disability upon release from multidrug therapy (MDT) in new cases of leprosy, registered at a referral center in Brazil. This is a longitudinal and retrospective study that evaluated 260 patients. Multivariate analyses, using both the ordinal logistic regression, as well as the classification and regression tree (CART) algorithm were performed to determine the factors associated with physical disability upon release from treatment. The prevalence of disability did not differ significantly between diagnosis and release from treatment. Number of affected nerves and sensory impairment upon diagnosis were risk factors for disability at the end of MDT. The analysis using the CART algorithm resulted in the development of a clinical score to predict the risk of disability upon release from MDT. The decision tree may have a direct applicability in clinical practice for professionals dealing with leprosy, as it allows them to identify patients with a higher risk of physical disability through the use of simple and widely available clinical tests. This study also shows that the disability grade upon admission is the main risk factor for disability upon release from MDT. This result draws attention to the importance of early diagnosis in disability prevention.