The efficacy of anticoagulation in reducing the risk of cardiogenic embolism has been demonstrated in patients with atrial fibrillation (AF), but there are few prospective studies assessing the influence of anticoagulation stability on ischemic stroke in such patients. Accordingly, the present study investigated prospectively whether an instability of the anticoagulation intensity would affect the efficacy of the therapy in a total of 156 patients with non-rheumatic AF (NRAF) who received oral anticoagulation with warfarin. During a 2-year follow-up period, the annual event rate of ischemic stroke was 2.1%. In patients without a history of prior stroke, no ischemic stroke occurred at a higher international normalized ratio (INR ≥2.0). In contrast, patients who had had a prior stroke had no INR-dependent reduction of incidence. The coefficient of variation (CV) of measured INRs was significantly greater in patients with ischemic stroke than in those without. By multivariate analysis, only greater CV (≥0.3) of INRs was an independent risk for ischemic stroke, although New York Heart Association functional class ≥ II and treatment with diuretics were of borderline significance by univariate analysis. The present results suggest that stability of anticoagulation intensity is important to protect thromboembolic events in patients with NRAF. (Jpn Circ J 2001; 65: 404 - 408)