It is unclear whether prior antidiabetic treatment affects stroke severity and outcome. To evaluate this association, we prospectively studied all patients who were admitted in our Department with acute ischaemic stroke (n = 378, mean age = 78.8 ± 6.5 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale. The outcome was assessed with the modified Rankin Scale at discharge and with in-hospital mortality. A total of 123 patients had type 2 diabetes mellitus. At admission, there was a trend for lower National Institutes of Health Stroke Scale in patients treated with dipeptidyl peptidase 4 inhibitors compared with patients treated with other antidiabetic agents (6.1 ± 7.5 vs 10.0 ± 9.2, respectively; p = 0.079). At discharge, patients treated with dipeptidyl peptidase 4 inhibitors had lower modified Rankin Scale than patients treated with other antidiabetic agents (2.1 ± 1.9 vs 3.2 ± 2.1, respectively; p < 0.05). Patients treated with dipeptidyl peptidase 4 inhibitors also had lower in-hospital mortality than patients treated with other antidiabetic agents (0.0% vs 15.1%, respectively; p < 0.05). In conclusion, prior treatment with dipeptidyl peptidase 4 inhibitors in patients with acute ischaemic stroke appears to be associated with better functional outcome and lower mortality risk.