Metabolic syndrome (MetS) has been associated with various chronic diseases which may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically-certified LTSA among Japanese workers. We recruited 67,403 workers (57,276 men and 10,127 women), aged 20-59 years, of 13 companies in Japan, during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and followed them up for LTSA events (≥ 30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) for LTSA associated with MetS and its components. During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41-1.68) among those with vs without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76), cardiovascular diseases (3.16), diseases of the musculoskeletal system and connective tissue (2.01), cancers (1.24), obesity-related cancers (1.35), mental, behavioral and neurodevelopmental disorders (1.28), reaction to severe stress and adjustment disorders (1.46) and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk. MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.