Background: Several reports suggest that stroke incidence is gradually declining, possibly owing to improvements in primary and secondary prevention. The objective of our study was to assess whether the trends of stroke hospitalization rates, common risk factors, and in-hospital outcomes affected both males and females similarly. Methods: A retrospective review was made of discharge letters of acute ischemic stroke hospitalizations during 1988, 1996, and 2006 in a tertiary referral hospital. Data regarding demographics, common risk factors, and the in-hospital outcomes were collected. Results: A total of 1,287 cases were recorded (mean age 68.7±11.8 years, 53.3% males). The annual age-adjusted rates of stroke hospitalizations per 1,000 persons in 1988, 1996, and 2006 were 2.31, 1.64, and 1.64, respectively (p<0.001). The age-adjusted rates decreased in males (3.0, 1.77, and 1.67; p<0.001); there was no significant trend among females (1.68, 1.53, and 1.62; p=0.864). The positive trends of age-adjusted rates of hypertension and dyslipidemia were significantly steeper in females than in males. No significant difference in the trends of adjusted in-hospital mortality rates between the sexes was found. Significant decline in the length of stay was demonstrated for both sexes, with no significant difference in the measure of decline between the groups. Conclusions: Stroke hospitalization rates decreased for men but not for women. Regardless of whether the discordance in stroke-incidence trends between males and females was caused by biological factors (different risk factor profile) or disparities in healthcare provision, it seems that the challenge of stroke prevention in the next decade is in lowering the risk of stroke in females.