Background and Objectives: Oral anticoagulants are the hallmark of cardioembolic stroke prevention, but they are frequently underused, especially in elderly patients and patients with paroxysmal atrial fibrillation. In our paper, we analyzed the long-term outcome of severely disabled cardioembolic stroke survivors depending on the prescribed antithrombotic secondary prevention medication. Materials and Methods: In our study, we retrospectively collected data for ischemic stroke (IS) patients treated in P. Stradins Clinical University hospital, Riga, Latvia, from 2014 until 2017. Patients’ clinical data were collected using local stroke registry, including patients’ demographic data, vascular risk factors, clinical findings, and laboratory results. Severely disabled stroke survivors were followed up by phone at 30/90/180/365 days after discharge. Patients’ functional outcomes were assessed using the adapted version of The Rankin Focused Assessment−Ambulation. The collected data were compared in 4 groups according to prescribed secondary prevention medication. Results: A total of 682 (91.42%) patients were followed up and included in data analysis. The median age of patients was 80 (IQR = 75−85) years. Of these patients, 231 (31%) were males and 515 (69%) were females. One-year probability of survival of patients not taking any preventive medication was 53% (IQR = 29−76), while in patients taking antiplatelet agents it was 57% (IQR = 37−78), 78% (IQR = 68−88) of patients on Vitamin K antagonists (VKA) and 81% (IQR = 72−90) in patients on direct oral anticoagulants (DOACs). One year after discharge 73 (31%) had mRS 0−2, 50 (20.9%), 29 (12.1%) were still severely disabled, and 87 (36.4%) had died. Conclusions: Anticoagulant use in secondary prevention predicts better functional outcome and higher survival rate in patients with severe cardioembolic stroke due to non-valvular atrial fibrillation (NVAF), therefore severe neurological deficit must not be a reason of restriction of anticoagulation.