We aimed to clarify the association between restfulness from sleep and subsequent risk of cardiovascular disease (CVD). Medical records of 1,980,476 individuals with neither prior history of CVD nor sleep disorders were extracted from the Japan Medical Data Center. Restfulness from sleep was subjectively assessed using information from the questionnaires at initial health check-ups. The mean age was 45 ± 11 years and 1,184,937 individuals were men. Overall, 1,197,720 individuals (60.5%) reported having good restfulness from sleep. The mean follow-up period was 1122 ± 827 days. Myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation occurred in 3673 (0.2%), 30,241 (1.5%), 13,546 (0.7%), 28,296 (1.4%), and 8116 (0.4%) individuals, respectively. Multivariable Cox regression analyses including age, sex, and other CVD risk factors after multiple imputation for missing values showed that good restfulness from sleep was associated with lower incidence of myocardial infarction (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.83-0.95), angina pectoris (HR 0.85, 95% CI 0.83-0.87), stroke (HR 0.85, 95% CI 0.82-0.88), heart failure (HR 0.86, 95% CI 0.84-0.88), and atrial fibrillation (HR 0.93, 95% CI 0.89-0.97). The association of restfulness from sleep with CVD events was pronounced in subjects with younger age and female sex. In conclusion, good restfulness from sleep may be associated with the lower risk of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Further studies are required to clarify the underlying mechanism and to develop a novel preventive approach for CVD from the perspective of sleep.