OBJECTIVE Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used in patients with rheumatic diseases, but their effects on the cardiovascular system remain unclear. We aimed to assess whether CQ/HCQ could reduce the risk of cardiovascular disease (CVD). METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the ClinicalTrials.gov for studies investigating the association between CQ/HCQ and the risk of CVD from inception to 20 December 2017. We carried out the quality assessment using the Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects model was used to pool the risk estimates relative ratio (RR), hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) for the outcomes. RESULTS A total of 19 studies (7 case-control studies, 12 cohort studies, and no clinical trials) involving 19,679 participants were included in the meta-analysis. Pooled results for HRs or RRs showed that CQ/HCQ was associated with a significantly reduced risk of CVD (pooled RR 0.72, 95% CI 0.56-0.94, p=0.013). Results based on ORs showed a similar tendency towards a reduced risk of CVD with CQ/HCQ (pooled OR 0.41, 95% CI 0.25-0.69, p=0.001). CONCLUSIONS Our results suggested that CQ/HCQ was associated with a reduced risk of CVD in patients with rheumatic diseases. Randomized trials are needed to confirm the potential of CQ/HCQ in cardiovascular prevention in patients with and without rheumatic diseases.