The addition of trastuzumab to chemotherapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) prolongs overall survival (OS) in clinical trials. However, treatment patterns and survival in daily practice are unknown. This study aims to compare trastuzumab use and outcome in HER2-positive MBC patients in a population-based cohort with clinical trial cohorts, with a special focus on elderly patients. MBC patients treated with trastuzumab-based chemotherapy in north-east Netherlands between 2005 and 2009 were identified from 23 hospital pharmacies and the Netherlands Cancer Registry. Baseline, treatment, and survival characteristics (Kaplan-Meier analysis) were compared with those found in clinical trials and differences in patients aged less than 65 versus 65 years or more were studied. Of 225 HER2-positive MBC patients (median: 54.8 years), 130 were treated with first-line trastuzumab. In first-line treatment, the median treatment duration was 9 months and the median OS was 30.7 months, which is comparable with the OS of 31.2 months found in a clinical trial with comparable baseline characteristics. In 25 patients aged 65 years or more compared with those aged less than 65 years treated with first-line trastuzumab, patients with a history of early breast cancer had less often been treated with adjuvant chemotherapy (36 vs. 71%; P = 0.001). Other baseline characteristics and OS were similar. Patient, treatment, and survival characteristics in a HER2-positive MBC population-based cohort share considerable similarities to those found in clinical trials. The influence of age on trastuzumab treatment was not detected.