Introduction: In Germany, stroke is the third leading cause of death, with more than 60,000 fatalities out of approximately 260,000 cases (first-ever and recurrent strokes) each year. So far, there are only a few long-term studies investigating determinants of the natural course of the disease, especially in the era of mechanical thrombectomy. Materials and Methods: The prospective single-center stroke cohort Augsburg (SCHANA) study will include about 1000 patients treated for stroke in the University Hospital of Augsburg. Patients aged 18 years or older with a confirmed diagnosis of ischemic or hemorrhagic stroke are included in the study. Information on demographic characteristics, onset of symptoms, etiologic factors, comorbidities, quality of life, invasive and non-invasive treatment, complications, and laboratory parameters are collected during a personal interview conducted during the patients’ hospital stay and via a medical chart review. About 30 mL of blood is collected from each patient, and after processing and aliquoting, all blood specimens are frozen at −80° C. The study participants will be followed-up via postal questionnaires at three and 12 months after discharge from the hospital. Furthermore, mortality follow-ups will be conducted. Cox-regression analysis will be used to estimate relative risks. Conclusion: The SCHANA study will generate comprehensive data on the long-term course of the disease. In addition to the main outcomes, recurrent events and survival, patient-oriented outcomes such as health-related quality of life and depression are the focus of the study.