Background: Synovial sarcoma (SS) accounts for 5-10% of all soft tissue sarcoma. SS are aggressive tumors with a median 5-year survival of 60-70% when localized disease but also a propensity for metastatic spread with 40-45% of patients developing metastasis within 5 years. It is considered a chemotherapy-sensitive sarcoma and treatment options are increasing. Herein, we present the outcomes of SS patients by systemic regimen and multimodality approach. Methods: This is a single institution, retrospective cohort of 79 patients with histopathologically confirmed SS treated at from 2004 to 2019. Clinical characteristics, treatment, response and survival were analyzed. We estimated medians of progression-free survival (PFS) and overall survival (OS) using the method of Kaplan-Meier along with the Log-Rank test. All tests were two-sided and statistical significance was considered when p<0.05. Results: Median follow-up was 3.7 years (range 3.13 to 4.33), 59.5% were women and median age at diagnosis was 41 (range 5-77). At presentation, 60 patients (75.9%) had localized disease and 19 (24.1%) presented with metastatic disease. Among the entire cohort the three-year OS rate was 78.9% (95%CI = 66.3-87.3) and five-year OS rate 68.7% (95%CI = 53.5-79.9). OS between localized disease (N = 45) and metastatic (N = 12) was not statistically significant (log-rank p = 0.098). When comparing different regimens, doxorubicin-based regimens (DBR) showed longest median PFS of 10.1 months (95%CI = 3.97-21.16), while pazopanib had a median PFS of 7.45 (95%CI = 2.63-12.3), high dose ifosfamide (HDI) 6.4 months (95%CI = 2.79-15.5) and trabectedin 3.12 months (95%CI = 0.99-6.97). Conversely, patients with metastatic disease treated with pazopanib experienced a median PFS of 11.47 months (95%CI = 2.63-32.9) while those treated with a DBR 8.15 months (95%CI = 1.08-35.8). Conclusions: SS is highly aggressive and, in our cohort, patients with local presentation had non-significant difference in OS to the metastatic disease, this could be due to a small sample size or the high probability for relapse this tumor has. Chemotherapy with DBRs showed superiority to other regimens and pazopanib showed to be slightly superior when evaluating only metastatic disease. Addition of pazopanib maintenance therapy may improve PFS and OS. Continuous evaluation of these patients with further inclusion of SS on immunotherapy is warranted.