While long-term anticoagulation prevents ischemic stroke in high-risk patients with atrial fibrillation (AF), the optimal initial anti-thrombotic regime in acute AF is less well defined. We randomized 96 patients with new onset acute AF in an emergency admission ward to receive (1) once-daily preparation of low molecular weight heparin (LMWH), tinzaparin or (2) conventional intravenous unfractionated heparin (target APTT 50-70 s). 5 patients in unfractionated heparin group compared with no patients in LMWH group (0%, P = 0.04) developed ischemic stroke/transient ischemic attack during the first 48 h. An initial subcutaneous LMWH was safe and effective in ischemic stroke prevention in patients with acute AF.