Little is known about the relationship of the difference between morning and evening systolic blood pressure (BP) (MEdif) in home BP with cardiovascular disease (CVD) incidence. To assess this relationship, we used data from the nationwide practice-based J-HOP (Japan Morning Surge-Home BP) study, which recruited 4258 cardiovascular risk participants (mean age 64.9 years; 46.8% men; 79.2% using antihypertensive medications) who underwent morning and evening home BP monitoring using a validated, automated device for 14 consecutive days. During a mean +/- SD follow-up of 6.2 +/- 3.8 years (26,295 person-years), 269 CVD events occurred. Adjusted Cox models suggested that higher MEdif (>= 20 mmHg) was associated with higher CVD risks than was medium MEdif (0-20 mmHg) independent of the average morning and evening (MEave) home systolic BP (SBP) (adjusted hazard ratio [HR]: 1.40; 95% confidence interval [CI] 1.02-1.91). We also divided participants into four BP phenotype groups as follows: "both non-elevated" (MEdif < 20 mmHg and MEave SBP < 135 mmHg), "elevated-MEdif" (MEdif >= 20 mmHg and MEave SBP < 135 mmHg), "elevated-MEave" (MEdif < 20 mmHg and MEave SBP >= 135 mmHg), and "both elevated" (MEdif >= 20 mmHg and MEave SBP >= 135 mmHg). The cumulative incidence of CVD events was higher in patients with the "elevated-MEdif," "elevated-MEave," and "both elevated" phenotypes than in those with the "both non-elevated" phenotype. After adjusting for covariates, the "both elevated" phenotype was associated with higher CVD risk than the "both non-elevated" phenotype (adjusted HR: 1.64; 95% CI: 1.09-2.46). This is the first study demonstrating a direct correlation between CVD outcomes and the difference between morning and evening home SBP. The present study demonstrated that the higher difference of morning and evening home systolic blood pressure (SBP) (MEdif: morning minus evening home SBP >= 20 mmHg) was associated with higher total cardiovascular disease (CVD) events risk compared with other MEdif groups. After adjusting confounding factors and average of morning and evening home SBP (MEave), the higher MEdif group showed higher CVD risk compared with the normal MEdif group (0-20 mmHg) (adjusted hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.01-1.88). The both elevated MEave (>= 135 mmHg) and MEdif (>= 20 mmHg) groups were also associated with higher CVD risk compared to the both controlled groups (adjusted HR 1.64, 95% CI 1.10-2.47). From these findings, the higher MEdif in home BP monitoring was suggested to predict future CVD incidence.