Introduction: The clinical outcomes of leprosy include complications such as physical disabilities and deformities that vary according to the degree of impairment of nerve trunks. Knowledge of the factors that lead to the development of these complications is important for disability prevention programs. This study aimed to evaluate clinical factors associated with the occurrence of physical disability in leprosy cases. Methodology: This was a retrospective study of 2,358 cases of leprosy in Aracaju, northeast Brazil, between 2001 and 2011. Analysis was done using the Chi-square test and logistic regression model. Results: Significant factors associated with disability were found to be male gender, having more than two affected nerves, multibacillary leprosy classification, leprosy reaction, and lepromatous leprosy. The multivariate analysis revealed that the associated factors included having more than two affected nerves, leprosy reaction (adjusted odds ratio [aOR]: 2.02, 95% confidence interval [CI]: 1.36 to 3.01), the multibacillary form (aOR: 2.74, 95% CI: 1.84 to 4.08), and lepromatous leprosy (aOR: 4.87, 95% CI: 2.86 to 16.08). Conclusions: The number of affected nerves, leprosy reaction, operational classification, and clinical presentation were identified as the main factors associated with the development of disability in leprosy patients.