Oral hypoglycemic drugs for type 2 diabetes aim at preventing the metabolic effects of hyperglycemia and cardiovascular (CV) events. The evidence of the possible CV risk related to the prescription of some antidiabetic drugs prompted regulatory agencies to require safety studies. This review provides an updated analysis of CV safety profiles for antidiabetic drugs used for the treatment of patients with high CV risk.The most recent studies analyze different aspects of CV morbidity, such as ischemic events, heart failure and arrhythmia, and their interactions with hyperglycemia. The endpoints include major adverse cardiovascular events (CV mortality, myocardial infarction, stroke) and hospitalization for heart failure. There is extra-and intra-class variability of CV risk among different oral hypoglycemic drugs, including sulfonylureas, metformin, glitazones, glucagon-like peptide-1 analogues, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors. Different treatment settings, selectivity towards pharmacological targets and hypoglycemia-related effects may explain the discrepancies observed.This review may guide cardiologists and diabetologists, in collaboration with general practitioners, to make the most appropriate therapeutic decision fitting the characteristics of the individual diabetic patient.