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The World Health Organization (WHO) 2016-2020 Global Leprosy Strategy aims to reinvigorate efforts to control leprosy and avert leprosy disability to less than 1 per million population.To systematically identify clinical factors associated with physical disability in patients with leprosy.Searches were conducted in Scopus, PubMed, and Web of Science databases to identify studies published from January 23, 1988, to May 23, 2018, using the keywords leprosy and physical disability and related terms.Studies that evaluated patients using the WHO leprosy disability grading system and reported the number of patients with and without disability by clinical characteristics were included.The odds ratio (OR) was used as a measure of association between the clinical features and physical disability. Summary estimates were calculated using random-effects models.The primary outcome was physical disability according to the WHO disability classification. The association between clinical features and physical disability was evaluated.The search identified 2447 reports. After screening titles and abstracts, 177 full-text articles were assessed for eligibility, and 32 studies were included in the systematic review; 24 of the 32 studies included sex information (39 571 patients), of whom 24 218 (61.2%) were male. Male patients with leprosy were more likely to have physical disability than female patients with leprosy (pooled OR, 1.66; 95% CI, 1.43-1.93; I2, 81.3%; P < .001). Persons with multibacillary leprosy were 4-fold more likely to have physical disability than those with paucibacillary leprosy (pooled OR, 4.32; 95% CI, 3.37-5.53; I2, 88.9%, P < .001). Patients having leprosy reactions were more likely to have disability (pooled OR, 2.43; 95% CI, 1.35-4.36; I2, 92.1%; P < .001). Patients with lepromatous leprosy experienced 5- to 12-fold higher odds of disability.This systematic review and meta-analysis confirms the association between the presence of physical disabilities and male sex, multibacillary leprosy, leprosy reactions, and lepromatous presentation. These findings can guide the development of targeted interventions for early identification of individuals at greater risk of developing physical disabilities and education campaigns to promote early consultation to institute treatment for leprosy reactions and prevent physical disability.