Patients with severe mental illness (SMI) have been described at higher risk of cardiovascular disease (CVD). The aim of this systematic review and meta-analysis was to quantify prevalence, incidence, cross-sectional association and longitudinal increased risk of coronary heart disease (CHD), stroke, transient ischemic attack and cerebrovascular disease (CBVD), heart failure (HF), peripheral vascular disease (PVD), death due to CVD, and any CVD in patients with SMI. We included 92 studies, with a total population of 3,371,461 patients (BD = 241,226, MDD = 476,102, SCZ = 1,721,586, SMI = 932,547) and 113,925,577 controls. Pooled prevalence of any CVD in SMI was 9.9% (95% CI = 7.4–13.3) (33 studies, 360,144 patients). Compared to controls, after adjusting for a median of 7 confounders, SMI was associated with higher risk of CVD in cross-sectional studies, OR:1.53 (95% CI = 1.27–1.83) (11 studies), with CHD OR: 1.51 (95% CI = 1.47–1.55) (5 studies), with CBVD OR: 1.42 (95% CI = 1.21–1.66) (6 studies), and tended to be associated with HF OR: 1.28 (95% CI = 0.99–1.65) (4 studies). Cumulative incidence was 3.6 CVD events in a median follow-up period of 8.4 years (range: 1.76–30). After considering a median of 6 confounders, SMI was associated with higher longitudinal risk of CVD in longitudinal studies HR: 1.78 (95% CI = 1.6, 1.98) (31 studies), of CHD: HR: 1.54 (95% CI 1.30–1.82) (18 studies), of CBVD HR: 1.64 (95% CI 1.26–2.14) (11 studies), of HF HR:2.10 (95% CI 1.64–2.70) (2 studies), of PVD, unadjusted RR: 3.11 (95% CI 2.46–3.91) (3 studies), of death due to CVD, HR 1.85 (95% CI 1.53–2.24) (16 studies). In this meta-analysis, the association between SMI and CVD has been quantified in a world representative sample; we suggest prevention of CVD should be warranted as standard care in SMI.