Rosiglitazone has been proposed as a treatment strategy for type 2 diabetes mellitus (T2DM), and it could provide robust glucose-lowering capability with risk of cardiovascular events. We thus performed a systematic review and meta-analysis of controlled trials to assess the effect of this treatment on glycaemic control and cardiovascular events in patients with T2DM. We systematically search PubMed, Embase, and the Cochrane Central Register of Controlled Trials comparing rosiglitazone to other anti-diabetic treatments. These studies included randomised controlled trials (RCTs), cohort studies, and case-control studies that had treatment with at least six months of follow-up in patients with T2DM. We aimed to evaluate the long-term effect on cardiovascular risk of rosiglitazone compared with a basal insulin drug. The main outcomes included myocardial infarction, heart failure, stroke, cardiovascular mortality, and all-cause mortality. We included 11RCTs and four observational studies involving 20,079 individuals with T2DM allocated to rosiglitazone and a similar number to comparison groups of which only five compared rosiglitazone with placebo and collected data on cardiovascular outcomes. Among patients with T2DM, rosiglitazone is associated with a significantly increased risk of heart failure, with little increased risk of myocardial infarction, without a significantly increased risk of stroke, cardiovascular mortality, and all-cause mortality compared with placebo or active controls. Alternative methods to reduce the uncertainty in long-term pragmatic evaluations, inclusion of rosiglitazone in factorial trials, publication of cardiovascular outcome data from adverse event reporting in trials of rosiglitazone and a cardiovascular endpoint trial of rosiglitazone among people without diabetes.