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Introduction: Soft tissue sarcomas (STSs) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available after the conventional first-line regimen. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS. This led to a FDA approval in 2015, but real-world evidence is still required, complementary to the pivotal phase II and III trials. Methods: One hundred twenty-six patients with STS, treated by trabectedin between 2002 and 2019, were analyzed in this retrospective study, in two French centers. The effects of trabectedin on survival, response, and toxicity were described. All patients were tested for toxicities, and efficacy was assessed in patients exposed to at least 2 cycles of trabectedin. Results: Three median cycles were administered per patient (1–79). Among the 113 patients analyzed for efficacy, the median progression-free survival was 3.0 months (95% CI: 2.3–4.8), with an overall survival of 12.3 months (95% CI: 10.2–16.9). The rate of disease control was 46% at the end of treatment. Myxoid liposarcoma (n = 11) was the histology subtype that benefited most from this chemotherapy with median progression-free survival and overall survival of 13.3 months (95% CI: 2.3–18.7) and 27.8 months (95% CI: 3.2–64.7), respectively. Adverse events were manageable. Discussion and Conclusion: Efficacy of trabectedin is confirmed in terms of clinical benefit and low toxicity, especially for myxoid liposarcoma. Combinatory regimens are under clinical trials to optimize the place of this chemotherapy.