OBJECTIVE: We aimed to investigate associations between cardiovascular reactivity to acute stress and sickness absence among Japanese male and female workers, in a prospective study. METHODS: Among healthy employed Japanese workers who underwent mental health checks between 2006 and 2009, data of 111 participants were analyzed. Changes in blood pressure, pulse rate, peripheral blood flow (PBF), and heart rate variability (HRV) (high frequency [HF] and low frequency [LF]) were calculated using differences between the two tasks, mirror drawing stress [MDS] and a maze task, and the postperiod value. Sickness absence through March 2010 was followed up by mail survey (average follow-up 2.3 years). Logistic regression analysis was used, adjusting for lifestyle factors. RESULTS: Among 12 participants who took sickness absences, eight were owing to mental problems. Changes in the LF during the MDS and maze tasks and LF-to-HF ratio during the MDS task were positively associated with all sickness absences (odds ratio [OR], 95% confidence interval [CI]: 2.09, 1.03-4.22; 2.04, 1.09-3.82; and 3.10, 1.46-6.58, respectively). Changes in PBF during the MDS task were also associated with increased risk of sickness absence (OR, 95% CI: 2.53, 1.10-5.81). CONCLUSION: Cardiovascular reactivity to acute stress should be considered at workers\' health checks.