The aim of this study was to retrospectively evaluate the efficacy and safety of trabectedin treatment in patients with metastatic soft tissue sarcoma (STS) in the routine clinical setting. Further, the type and frequency of systemic treatments before commencing treatment with trabectedin and after its discontinuation, as well as the frequency of pulmonary metastasectomies, were analyzed. The current analysis includes retrospective data from consecutive STS patients treated with trabectedin at the Department of Medicine I, Division of Oncology, Medical University of Vienna, between January 2008 and December 2012. Patients were analyzed for median progression-free survival, overall survival (OS), and therapy-related toxicity. Data of 60 STS patients were included in the present analysis. In total, 198 cycles of trabectedin were administered, whereas the median number of cycles administered per patient was two (range 1–25). The median progression-free survival was 2.2 months and the median OS (mOS) was 11.8 months. mOS calculated from the first time point of detection of metastatic disease was 35.8 months. The 18 patients (30%) who underwent pulmonary metastasectomy had an mOS of 50.2 months. Further, trabectedin had a manageable toxicity profile comparable to data reported in previous phase II trials. Our findings support the use of trabectedin as an active and feasible therapeutic option among advanced, metastatic, and refractory STS patients. The good safety profile and lack of cumulative toxicity allow prolonged administration in highly pretreated patients. As visible from the present data, a considerable percentage of patients with advanced/metastatic STS benefit from sequential lines of drug therapy as well as pulmonary metastasectomy.