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Few studies have investigated the association between leisure-time physical activity and long-term medication use in Brazilian populations, especially those of low socioeconomic status. The objective of this study was to analyze the association between the need for long-term medication and leisure-time physical activity in adults from the Ermelino Matarazzo district, a low-income region in São Paulo, Brazil. A population-based cross-sectional study was conducted in 2007 and involved 890 subjects aged 18 years or older. Data regarding the need for long-term medication and types of medications used were collected using a questionnaire. Leisure-time physical activity was measured using the long version of the International Physical Activity Questionnaire. Descriptive analysis, chi-square test, and simple and multiple binary and multinomial logistic regression analysis were used. Among the subjects studied, 29.2% reported the need for long-term medication and 10% required at least two different types of medications. After adjustment for gender, age, education level and Body Mass Index, subjects who did not perform at least 150 min/week of leisure-time physical activity presented 2.78 (95% confidence interval - 95%CI: 1.45; 5.30) and 4.69 (95%CI: 1.90; 11.53) times the odds of requiring long-term medication and two or more types of medications rather than none, respectively, than those who did. Broader discussion of the interaction between medication, leisure-time physical activity and social and economic aspects is needed to reduce inequalities and to improve the health of individuals of low socioeconomic status.