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Alterations in hemostasis are linked to the development of ischemic stroke. Intrinsic coagulation pathway activity is typically assessed via Activated Partial Thromboplastin Time (APTT). This study investigates the association between shortened APTT duration and ischemic stroke development. This retrospective case-control study included 85 patients with acute ischemic stroke who were admitted to the Ibb University-affiliated Hospitals, from Jun 2022 to Sept 2023 and 35 control subjects with no history of stroke. Shortened APTT was defined with a duration lower than 28.4 seconds. Multivariate analysis was conducted analyzing factors associated with acute ischemic stroke using Odds Ratio (OR) and 95% Confidence Interval (CI). The mean age of control subjects and acute ischemic stroke cases was 40.69±8.28 years and 62.08±12.19 years, with female gender present in 10 (28.6%) and 41(48.2%) respectively. In the multivariate regression, advanced age (OR: 1.21; 95% CI: 1.13-1.30), APTT less than 28.4 seconds (OR: 7.61; 95% CI: 2.85-20.32), hypertension (OR: 28.74; 95% CI: 6.45-128.04), diabetes mellitus (OR: 10.96; 95% CI: 4.06-29.59), family history of cerebrovascular disease (OR: 13.37; 95% CI:1.73-103.27), current smoking status (OR: 2.48; 95% CI:1.09-5.64), higher cholesterol level (OR: 1.01; 95% CI:1.00-1.02), higher triglycerides level (OR: 1.05; 95% CI:1.03-1.08), and higher LDL level (OR: 1.07 95% CI:1.04-1.10) were predictive factors for acute ischemic stroke occurrence and were statistically significant (all p