Background and objectives: Siesta, which is a short afternoon nap, is a habit that is commonly practiced in the Mediterranean and tropical areas. Data on the association between siesta and coronary artery disease has been conflicting. A protective effect has been demonstrated in the countries that commonly practice siesta, but a harmful effect has been observed in the countries that infrequently practice the siesta habit. Information on the association between siesta and ischemic stroke has been, however, lacking. Hence, the purpose of our study was to determine the effect of siesta on ischemic stroke. Materials and Methods: This was a case-control study, conducted on the patients with acute ischemic stroke who came for their first follow-up visit to the neurology clinic. Controls were randomly selected from the patients visiting the neurology clinic on the same day as the patients with ischemic stroke. In addition to basic demographics and the occurrence of established stroke risk factors, information about siesta practice was also collected from both groups. A multivariate logistic regression analysis was utilized to determine the relationship between siesta practice and ischemic stroke. Results: A total of 206 patients were recruited from the neurology clinic of King Khalid university hospital / of which only 194 subjects were included in the analysis (98 ischemic stroke cases and 96 controls). The mean age of the participants was 59.68 ± 13.75 years and 98 (50.52%) were male. Interestingly, 43% of the whole study cohort practiced regular siesta. However, when compared to the stroke population, the control group practiced siesta more frequently (30% vs. 56%). In a multivariate logistic regression analysis, hypertension, diabetes mellitus, excess body weight (body mass index > / 25 kg/m2) and dyslipidemia were found to increase the risk of ischemic stroke (OR 2.12, 95% CI: 1.02–4.66, p = 0.005 / OR 2.72, 95% CI: 1.94–4.88, p = 0.014 / OR 2.94, 95% CI: 1.5164–5.7121 p = 0.0014 / OR 3.27, 95% CI: 2.42–5.199, p ≤ 0.001, respectively). On the contrary, the practice of regular siesta lowered the risk of ischemic stroke (OR 0.58, 95% CI: 0.3551–0.9526, p = 0.031). Conclusions: Siesta was associated with a reduced risk for the occurrence of ischemic stroke. Large prospective longitudinal studies should be conducted to verify the protective effect of siesta on stroke.