Background: Synovial sarcoma is a relatively chemosensitive type of soft tissue sarcoma and it often metastasizes to the lung. We investigated the role of adjuvant chemotherapy in patients with high-grade synovial sarcoma at their first lung metastasectomy (LMTS). Methods: Forty-six HGSS patients had their first LMTS at our institute (Rizzoli Orthopedic Hospital, Bologna, Italy) between 2000 and 2020. We divided them into two groups: (1) those undergoing adjuvant chemotherapy (n = 24) and (2) those not receiving adjuvant chemotherapy (n = 22). The primary outcome was a median survival at 32.5 (IQR 18.0-82.7) median follow-up. The disease-free interval was calculated at time zero (DFI0, interval between the diagnosis of the primary tumor and the first CT-diagnosed lung metastasis) and at any further lung relapse (DFI1-3). T0 was defined as the time at first LMTS and T1-T3 referred to the time of further metastasectomy. Results: Freedom from SS-specific mortality at 60 months was significantly higher in patients without chemotherapy (50.0% (33.0-76.0%) vs. 20.8% (9.55%-45.4%), p = 0.01). Chemotherapy was associated with a higher risk of SS-specific mortality at multivariable Cox regression (HR 2.8, p = 0.02). Furthermore, DFI0 ≤ 6 months, female sex, age > 40 years, and primary tumor > 10 cm increased the risk of death by about four, six, >three, and >five times, respectively. Conclusions. Adjuvant chemotherapy did not show any advantage in terms of freedom from SS-specific mortality in HGSS patients. Further larger studies are necessary to confirm our findings.