Type 2 Diabetes (T2DM) is the most rapidly increasing risk factor for ischemic stroke. We aimed to compare trends in outcomes for ischemic stroke in people with or without diabetes in Spain between 2003 and 2012. We selected all patients hospitalized for ischemic stroke using national hospital discharge data. We evaluated annual incident rates stratified by T2DM status. We analyzed trends in the use of diagnostic and therapeutic procedures, patient comorbidities, and in-hospital outcomes. We calculated in-hospital mortality (IHM), length of hospital stay (LOHS) and readmission rate in one month after discharge. Time trend on the incidence of hospitalization was estimated fitting Poisson regression models by sex and diabetes variables. In-hospital mortality was analyzed using logistic regression models separate for men and women. LOHS were compared with ANOVA or Kruskal-Wallis when necessary. We identified a total of 423,475 discharges of patients (221,418 men and 202,057 women) admitted with ischemic stroke as primary diagnosis. Patients with T2DM accounted for 30.9% of total. The estimated incidence rates of discharges increased significantly in all groups. The incidence of hospitalization due to stroke (with ICD9 codes for stroke as main diagnosis at discharge) was higher among those with than those without diabetes in all the years studied. T2DM was positively associated with ischemic stroke with an adjusted incidence rate ratio (IRR) of 2.27 (95% CI 2.24–2.29) for men and 2.15 (95%CI 2.13–2.17) for women. Over the 10 year period LOHS decreased significantly in men and women with and without diabetes. Readmission rate remained stable in diabetic and non diabetic men (around 5%) while slightly increased in women with and without diabetes. We observed a significant increase in the use of fibrinolysis from 2002–2013. IHM was positively associated with older age in all groups, with Charlson Comorbidity Index > 3 and atrial fibrillation as risk factors. The IHM did not change significantly over time among T2DM men and women ranging from 9.25% to 10.56% and from 13.21% to 14.86%, respectively; neither did among non-diabetic women. However, in men without T2DM IHM decreased significantly over time. Diabetes was associated to higher IHM only in women (OR 1.07; 95% CI, 1.05–1.11). Our national data show that incidence rate of ischemic stroke hospitalization increased significantly during the period of study (2003–2012). People with T2DM have more than double the risk of ischemic stroke after adjusting for other risk factors. Women with T2DM had poorer outcomes- IHM and readmission rates- than diabetic men. Diabetes was an independent factor for IHM only in women.