Cardiovascular disease (CVD) risk in train drivers is associated with health conditions that can result in sudden incapacity. Drivers are at high risk on several CVD risk factors with research suggesting that sleep may predict CVD risk, however this relationship has not yet been explored. This study investigated the link between sleep and CVD risk, in relation to hours of work day and days off sleep. N=309 Australian drivers completed a cross-sectional survey. A CVD risk score was calculated by summing scores from behavioural and biomedical risk factors. Sleep was most frequently cited as the main reason for decline in perceived health status. Main analyses showed that shorter work day sleep (M=5.79 h) was a significant predictor of increased CVD risk (p=0.013). This relationship was moderated by days off sleep, such that when days off sleep (M=8.17 h) was higher, the effect of work day sleep on CVD risk was weaker (p=0.047). Findings indicate the amount of sleep a driver obtains on non-work days may compensate for adverse health outcomes. Successful management of fatigue in safety critical occupations appears essential not only for the prevention of safety hazards, but also for the long-term health of shift workers. Further investigation is warranted.