Different anthracycline-free regimens have demonstrated activity, without serious cardiac events. This study was conducted to evaluate the activity and toxicity of docetaxel and trastuzumab given every 21 days in patients with metastatic breast cancer (MBC). The primary endpoint was time to progression and the secondary aims included response rate, safety, duration of response, and overall survival. Eligible patients were those with MBC human epidermal growth factor receptor-2+ (HER2+) with no previous chemotherapy for advanced disease. Patients received six cycles of docetaxel (100 mg/m) plus trastuzumab (8 mg/kg loading dose and 6 mg/kg every 21 days thereafter), followed by maintenance treatment with trastuzumab monotherapy every 21 days until disease progression. Forty-nine patients with HER2+ MBC were included. The overall response rate was 44.9% (22/49). With a median follow-up of 16.6 months, the median time to progression was 8.3 months and the median overall survival was 25.7 months. Nineteen patients did not receive treatment continuation with trastuzumab monotherapy. The most common toxicity was febrile neutropenia. A total of 10 patients were taken off the study due to treatment-related toxicity, mainly cardiac events. First-line trastuzumab combined with docetaxel is an effective and well tolerated regimen for HER2+ MBC.