The high incidence of stroke recurrence necessitates effective post-stroke care. This study investigates the effectiveness of a case management-based post-stroke care program in patients with acute stroke and TIA. In this prospective cohort study, patients with TIA, ischemic stroke or intracerebral hemorrhage were enrolled into a 12-month case management-based program (SOS-Care) along with conventional care. Control patients received only conventional care. The program included home and phone consultations by case managers, focusing on education, medical and social needs and guideline-based secondary prevention. The primary outcome was the composite of stroke recurrence and vascular death after 12months. Secondary outcomes included vascular risk factor control at 12months. From 11/2011 to 12/2020, 1109 patients (17.9% TIA, 77.5% ischemic stroke, 4.6% intracerebral hemorrhage) were enrolled. After 85 (7.7%) dropouts, 925 SOS-Care patients remained for comparative analysis with 99 controls. Baseline characteristics were similar, except for fewer males and less frequent history of dyslipidemia in post-stroke care. At 12 months, post-stroke care was associated with a reduction in the composite endpoint compared to controls (4.9 vs. 14.1%; HR 0.30, 95% CI 0.16-0.56, p < 0.001), with consistent results in ischemic stroke patients alone (HR 0.32, 95% CI 0.17-0.61, p < 0.001). Post-stroke care more frequently achieved treatment goals for hypertension, dyslipidemia, diabetes, BMI and adherence to secondary prevention medication (p < 0.05). Case management-based post-stroke care may effectively mitigate the risk of vascular events in unselected stroke patients. These findings could guide future randomized trials investigating the efficacy of case management-based models in post-stroke care.