BACKGROUND: Few studies have investigated the association between tobacco smoking and sick leave (SL) in Japan. METHODS: We followed 70,896 workers aged 20-59 years (60,133 males, 10,763 females) between April 2012 and March 2017. A Cox proportional hazards model was used to investigate the associations between smoking (smoking status and intensity) and long-term SL (i.e., SL lasting ≥ 30 consecutive days). Cause-specific analyses were also conducted. RESULTS: A total of 1,777 people took long-term SL during a follow-up of 307,749 person-years. Compared with never smokers, current smokers were at a higher risk of long-term SL (hazard ratio [HR] = 1.31; 95% confidence interval [CI] = 1.17-1.46). Cause-specific analyses revealed that current smoking was associated with a higher risk of SL due to all physical disorders (HR = 1.42, 95% CI = 1.21-1.67), cancer (HR = 1.49, 95% CI = 1.10-2.00), cardiovascular disease (CVD; HR = 2.09, 95% CI = 1.26-3.45), and external causes (HR = 1.84, 95% CI = 1.31-2.59). Former smokers were at a higher risk of SL due to cancer at a borderline significance level (HR = 1.37, 95% CI = 0.98-1.91). Low-intensity smoking (i.e., 1-10 cigarettes smoked per day) was associated with all-cause SL, SL due to CVD, and SL due to external causes, compared with never smokers. CONCLUSION: In a large cohort of working-age Japanese, smoking was associated with a greater risk of long-term sick leave. Greater effort is needed to mitigate disease burden associated with smoking at workplace in Japan. IMPLICATIONS: Our study contributes to the literature on the association between smoking and sick leave in several ways. First, the study was conducted among a Japanese working population. While the association has been extensively studied in Western setting, few attempts have been made elsewhere. Second, cause-specific analyses were undertaken in our study. Third, we paid attention to the effect of low-intensity smoking on sick leave given that there is growing evidence of an elevated health risk associated with low-intensity smoking.