Abstract Background Stroke is the leading cause of adult disability and mortality in Taiwan, resulting in a tremendous burden on the healthcare system. The purpose of this study was to characterize disease burden by evaluating readmissions, mortality, and medical cost during the first year after acute stroke under the National Health Insurance (NHI) program. Methods This retrospective cohort study extracted information about patients hospitalized with acute stroke from claims data of 200,000 randomly sampled NHI enrollees in Taiwan, with a 1-year follow-up duration. The incidence of the first-year adverse events (AEs) indicated by readmissions or mortality, and the amount of the first-year medical cost (FYMC) were assessed with predictive factors explored. Additionally, we also estimated the cost per life and life-year saved. Results There were 2368 first-ever stroke patients in our study, including those with subarachnoid hemorrhage (SAH) 3.3%, intracerebral hemorrhage (ICH) 17.9%, ischemic stroke (IS) 49.8%, and transient ischemic attack/other ill-defined cerebrovascular diseases (TIA/unspecified) 29.0%; each stroke type was identified with an all-cause AE of 59.0%, 63.0%, 48.6%, and 46.8%, respectively. Readmissions were mainly because of acute recurrent stroke or the late effects of previous stroke, respiratory disease/infections, heart/circulatory disease, and diseases of the digestive system. Advanced age, hemorrhagic stroke type, respiratory distress/infections, and greater comorbidities were predictive of increased AE risk. Admission to neurology/rehabilitation wards, undertaking neurosurgery, or use of inpatient/outpatient rehabilitation was less likely to incur AEs. Initial hospitalization, readmission, and ambulatory care constituted 44%, 29%, and 27%, respectively, of FYMC with the initial length of stay being the most reliable predictor. The FYMCs were NT $217,959, $246,358, $168,003, and $122,084 for SAH, ICH, IS, and TIA/unspecified, respectively. The cost per life saved were estimated to be NT $435,919, $384,028, $196,281, and $138,888, whereas cost per life-year saved were estimated to be NT$43,926, $48,019, $97,830, and $188,770 for SAH, ICH, IS, and TIA/unspecified, respectively. Conclusion Half of the patients encountered readmission or death during the first year after stroke. Patients with advanced age, more complications, or comorbidities during initial stay tended to be highly vulnerable to AE occurrence, whereas TIA/unspecified stroke carried no less risk for AEs. FYMC or estimated cost per life saved for IS or TIA/unspecified was lower relative to SAH or ICH; however, their estimated cost per life-year saved became higher because of reduced life expectancy.