OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of direct percutaneous transluminal angioplasty (PTA) for patients with acute middle cerebral artery (MCA) trunk occlusion. METHODS Over the past 9 years, a total of 70 patients with acute MCA trunk occlusion were treated with intra-arterial reperfusion therapy. In the last 5 years, 34 patients were treated with direct PTA, and subsequent thrombolytic therapy was added if necessary for distal embolization. The other 36 patients, mainly in the first 4 years, were treated with thrombolytic therapy alone and were used as controls. Pretherapeutic neurological status was evaluated with National Institutes of Health Stroke Scale scores. The modified Rankin Scale (mRS) was used to assess clinical outcome at 90 days. RESULTS There were no significant differences in pretherapeutic National Institutes of Health Stroke Scale score and duration of ischemia between the 2 groups. The rate of partial or complete recanalization in the PTA group was 91.2%, whereas that in the thrombolysis-alone group was 63.9% (P<0.01). The incidence of large parenchymal hematoma with neurological deterioration in the PTA group was 2.9%, while that in the thrombolysis-alone group was 19.4% (P=0.03). Although direct PTA did not improve the rate of favorable outcome (mRS score 0 or 1; 41.7% for the thrombolysis-alone group versus 52.9% for the PTA group; P=0.48), outcome in terms of independence (mRS score 0, 1, 2) was significantly better in the PTA group (73.5%) than in the thrombolysis-alone group (50.0%; P=0.04). CONCLUSIONS Although definitive conclusions on the comparative merits of these 2 therapies cannot be drawn because of an open trial, direct PTA may be an effective alternative option to intra-arterial thrombolysis for acute MCA trunk occlusion.