To evaluate the cost-saving of a specialized, eHealth-based management service (CS) in comparison to regular medical care (RMC) for the management of patients receiving oral anticoagulation (OAC) therapy. Costs of hospitalization were derived via diagnosis-related groups which comprise diagnoses (ICD-10) and operation and procedure classification system (OPS), which resulted in OAC-related (i.e. bleeding/ thromboembolic events) and non-OAC-related costs for both cohorts. Cost for anticoagulation management comprised INR-testing, personnel, and technical support. In total, 705 patients were managed by CS and 1490 patients received RMC. The number of hospital stays was significantly lower in the CS cohort compared to RMC (CS: 23.4/100 py; RMC: 68.7/100 py); with the most pronounced difference in OAC-related admissions (CS: 2.8/100 py; RMC: 13.3/100 py). Total costs for anticoagulation management amounted to 101 EUR/py in RMC and 311 EUR/py in CS, whereas hospitalization costs were 3261 [IQR 2857-3689] EUR/py in RMC and 683 [504-874] EUR/py in CS. This resulted in an overall cost saving 2368 EUR/py favoring the CS. The lower frequency of adverse events in anticoagulated patients managed by the telemedicine-based CS compared to RMC translated into a substantial cost-saving, despite higher costs for the specialized management of patients.Trial registration: ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.