Background: Previous trials indicated that intensive glucose lowering in treatment of patients with type 2 diabetes mellitus (T2DM) was associated with a higher incidence of mortality. We therefore conducted a meta-analysis to evaluate the benefits and harms of intensive glucose lowering therapy in treatment of T2DM patients on major cardiovascular outcomes. Methods: Randomized controlled trials (RCTs) were obtained from searches of PubMed, EmBase, and the Cochrane Library electronic databases until Feb. 2016. Relative risk (RR) was used to measure the treatment effect by random-effect model. Meta-regression, sensitivity analyses, subgroup analyses, and publication biases were also conducted. Results: Thirteen RCTs were included with 58,160 T2DM patients and reported 5719 major cardiovascular events (MACEs), 6569 deaths, 2057 cardiac death cases, 3201 myocardial infarction (MI) cases, 1835 stroke cases, and 1778 congestive heart failure cases. Intensive glucose lowering therapy significantly reduced risk of MACEs (RR: 0.92; 95% CI: 0.85-1.00; P = 0.042), and MI (RR: 0.90; 95% CI: 0.82-0.98; P = 0.020) compared with conventional glucose control therapy. Furthermore, intensive glucose lowering therapy has no significant effect on the incidence of total mortality (RR: 0.98; 95% CI: 0.91-1.07; P = 0.693), cardiac death (RR: 1.00; 95% CI: 0.87-1.04; P = 0.999), stroke (RR: 0.94; 95% CI: 0.84-1.06; P = 0.333), and congestive heart failure (RR: 1.19; 95% CI: 0.96-1.48; P = 0.108). Conclusion: T2DM patients who received intensive glucose lowering therapy are associated with a reduced risk of MACEs and MI, whereas it has no significant effect on the risk of total mortality, cardiac death, stroke, and congestive heart failure. These effects might differ when stratified by baseline characteristics in T2DM patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.