Introduction Some available experimental studies have reported that hydrophilic statins might have advantages compared with lipophilic statins in patients with coronary artery disease (CAD). Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) investigating the potential differences of lipophilic and hydrophilic statins in patients with CAD. Methods We systematically searched selected electronic databases up to September 2016 to select RCTs, which compared clinical outcomes of hydrophilic vs lipophilic statins. Primary endpoints were cardiovascular (CV) events: major adverse cardiac events, myocardial infarction, cardiac revascularization, stroke, CV death, CV hospitalization, and all-cause mortality. Secondary endpoints were safety parameters: drug discontinuation, statin-associated muscle symptoms and alanine aminotransferase level increase. Results A total of 11,697 patients from 11 RCTs, randomly allocated to lipophilic (n = 5736) or hydrophilic statins (n = 5961), with a mean follow-up 14 months, were included in the meta-analysis. In comparison with hydrophilic, the lipophilic statins showed similar risk reduction for major adverse cardiac events (relative risk = 0.969, 95% confidence interval [CI], 0.835–1.125, P = .682), myocardial infarction (0.880, 95% CI: 0.731–1.058, P = .174), CV death (0.757, 95% CI: 0.486–1.180, P = .219), and all-cause mortality (0.797, 95% CI: 0.590–1.075, P = .137), as well as cardiac revascularization, stroke, drug discontinuation, and statin-associated muscle symptoms. CV hospitalization was lower (0.789, 95% CI: 0.643–0.969, P = .024) and alanine aminotransferase elevation was higher (2.689, 95% CI: 1.841–3.954, P ≤ .001) in lipophilic than in hydrophilic-treated patients. Conclusions In conclusion, similarity between hydrophilic and lipophilic statins holds between various clinical CAD settings.