We created an algorithm for diagnosing subtypes of cerebral infarction (CI) during the acute stage by combining atrial fibrillation (AF) and D-dimer levels. One-hundred and eight patients hospitalized for acute CI were retrospectively analyzed. CI was classified into cardioembolic, atherothrombotic, lacunar infarction or others. Patients were classified in AF group if they had AF on admission or a prior history of AF. This group was diagnosed to suffer cardioembolic infarction. In non-AF group, cardioembolic infarction was diagnosed when D-dimer level exceeded the cutoff point determined using a receiver operating curve. Then, usefulness of the algorithm was validated prospectively in 259 consecutive patients with acute CI. For the retrospective group, cardioembolic infarction was found in 82% of the AF group. In non-AF group, cardioembolic infarction was found in only 2%, when D-dimer level was <1.6 microg/ml. However, 41% of non-AF group with atherothrombotic infarction had elevated D-dimer level (> or =1.6 microg/ml). Results for the validation group were similar to those for the retrospective group (sensitivity, 89%; specificity, 66%; positive predictive value, 50%; and negative predictive value, 94%). D-dimer level in combination with AF can be useful for distinguishing CI subtypes during the acute stage.