Background: Cardiovascular disease is the leading cause of mortality among adults with Type 2 diabetes. The thiazolidinediones including rosiglitazone are approved for the treatment of Type 2 diabetes on the basis of their ability to lower blood sugar and surrogate markers of cardiovascular disease. Objectives: To ascertain the cardiovascular, skeletal and hematologic safety profile of rosiglitazone. Methods: Synthesis of evidence from recent trials, systematic reviews, meta-analysis, regulatory documents and clinical trials registries of manufacturers. Conclusion: Rosiglitazone increases the risk of heart failure, myocardial infarction and fractures (in women) with Type 2 diabetes.