Abstract Background The results of observational studies evaluating and comparing the cardiovascular safety of glitazones, metformin and sufonylureas are inconsistent.To conduct and evaluate heterogeneity in a meta-analysis of observational studies on the risk of acute myocardial infarction (AMI) or stroke in patients with type 2 diabetes using non-insulin blood glucose–lowering drugs (NIBGLD). Methods We systematically identified and reviewed studies evaluating NIBGLD in patients with type 2 diabetes indexed in Medline, Embase, or the Cochrane Library that met prespecified criteria. The quality of included studies was assessed with the RTI item bank. Results were combined using fixed- and random-effects models, and the Higgins I 2 statistic was used to evaluate heterogeneity. Sensitivity analyses by study quality were conducted. Results The summary relative risk (sRR) (95 % CI) of AMI for rosiglitazone versus pioglitazone was 1.13 (1.04–1.24) [I 2  = 55 %]. In the sensitivity analysis, heterogeneity was redu...