Uncertainty exists regarding cardiovascular (CV) safety of sulphonylureas (SUs) as reflected in package labels and treatment guidelines. This study evaluated clinical treatment practice for SUs by analysing prescription patterns for SUs relative to patient history of CV disease (CVD). Patients in Denmark initiating treatment with SU or other anti-hyperglycaemic drugs during 2006–12 were retrospectively identified using national health registries. Pre-existing (previous 12 years) overall CVD, coronary heart disease (CHD) and myocardial infarction (MI) were subsequently identified. Proportion of patients with pre-existing CVD was compared between new users of SU and new users of other anti-hyperglycaemic drugs. In total, 50,425 (42.2% females, mean ± SD age 63.3 ± 13.5 years) and 190,438 (46.5% females, age 60.3 ± 15.0 years) patients initiated treatment with SU or other anti-hyperglycaemic drugs, respectively, during 2006–12. The number of patients initiating SU treatment decreased by 63% during 2006–12. The proportion of patients with pre-existing CVD varied between 46.9% and 49.8% among new SU users versus 39.9% and 44.8% among new users of other anti-hyperglycaemic drugs. Corresponding proportions for CHD (17.9–19.9% versus 15.4–16.9%) and MI (6.3–7.5% versus 5.8–6.2%) showed the same pattern. Excluding new gliclazide users (9.6% of all new SU users) from the SU definition did not alter the results. Despite a potentially increased CV risk associated with use of SUs, pre-existing CVD did not decrease clinicians’ relative prescriptions of SUs.