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To evaluate impact of working days lost and factors for developing sick leave episodes in Mexicans workers with rheumatoid arthritis (RA). A prospective cohort of 123 patients with RA was followed for 1 year. Factors evaluated for sick leave episodes included: demographics, job characteristics, comorbidity, depressive symptoms, and clinical/therapeutic variables. Rates of sick leave episodes, working days lost, and permanent work disability (PWD) were identified. Statistical analysis included Cox regression models estimating hazard risks (HR) and their 95 % confidence intervals (95% CI). Cumulative time of follow-up for the cohort was 43,380 days, 24 % of workers had at least one episode of sick leave, with a mean of working days lost per patient-year of 18.36; 4.1 % developed PWD. Development of sick leave in the Kaplan-Meier analysis was associated with: age ≥40 years (p = 0.04), having a couple (p = 0.04), performing manual work (p = 0.03), suffering depressive symptoms (p = 0.04), limitations in functioning (p = 0.01), and poor global functional status ≥ III (p = 0.01). Cox regression models identified HAQ-Di ≥ 0.6 as the stronger predictor for sick leave (HR = 4.04, 95 % CI 1.41-11.58, p = 0.009) followed by age (HR = 1.05, 95 % CI 1.01-1.11, p = 0.04), ≥4 risk factors had a HR to 9.4 (95 % CI: 2.1-42.7) for sick leave. In this prospective cohort of Mexican workers with RA, we identified several factors associated with sick leave episodes and working days lost that should be potentially addressed by a multidisciplinary approach, being required to revaluate these strategies with the aim of increasing the work permanence of these patients.