The purpose of this study was to test the hypothesis that direct percutaneous transluminal angioplasty (PTA) might reduce the incidence of haemorrhagic complications and might improve recanalization rate and clinical outcome as compared with intra-arterial (IA) thrombolysis in patients with acute middle cerebral artery (MCA) trunk occlusion. A total of 70 patients with acute MCA trunk occlusion were treated with IA reperfusion therapy. Thirty-six patients were treated with IA thrombolysis alone. In the other 34 patients, direct PTA was selected as the first choice of the treatment and subsequent thrombolysis was added if necessary for distal embolization. The modified Rankin scale (mRS) was used to assess clinical outcome at 90 days. As compared with IA thrombolysis, direct PTA provided significant increase in the rates of partial or complete recanalization (63.9 vs 91.2%, p < 0.01) and decrease in the incidence of large parenchymal hematoma with neurological deterioration (19.4% vs 2.9%, p=0.03). Despite such favorable effects, direct PTA did not improve the rate of a favorable outcome (mRS score 0 or 1, 41.7% for the IA thrombolysis group vs 52.9% for the PTA group, p=0.48). However, outcome classified in terms of independence (mRS score </= 2) was significantly better in the PTA group (73.5%) than the IA thrombolysis group (50.0%, p=0.04). In patients with acute MCA trunk occlusion, as compared with IA thrombolysis, direct PTA improved recanalization rate and reduced serious haemorrhagic complications, resulting in a significant increase in independent patients.