Background: From 2002 to 2007, we carried out a multicentric Italian/Spanish Phase 3 trial comparing 3 vs 5 cycles of adjuvant CT with full-dose epirubicin + ifosfamide in high-risk STS. A previous Italian randomized study had demonstrated a survival benefit with 5 cycles of the same CT vs nil (JCO 2001;19:1238). The results of this trial were reported (JCO 2012;30:850), with no difference between the two arms in terms of OS and RFS, at a median follow-up (FU) of 5 years. We herein update these results with a longer FU. Methods: Patients were randomized to receive 3 preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same 3 preoperative cycles plus 2 postoperative cycles (Arm B). Radiotherapy (RT) could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary endpoint, OS, was assessed by the confidence interval (CI) of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. Results: Between January 2002 and April 2007, 160 pts were assigned to arm A and 161 to arm B. 158 patients received preoperative RT (77 in Arm A and 81 in Arm B). At a median FU of 116 months (IQ range 102-130 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that 3 cycles were not inferior to 5 cycles (one-sided 95% upper confidence limit was 1.24). A per-protocol analysis confirmed these results. Distant metastases (DM) were observed in 114 patients, 57 in Arm A and 57 in Arm B. The 10-year crude cumulative incidence of DM from surgery was 34.5%, 34.1% in Arm A and 34.8% in Arm B. Conclusions: The updated results of this trial at a longer FU confirm the non inferiority of 3 cycles of a full-dose conventional CT in comparison to 5, with about 60% patients alive and disease-free in both arms at 10 years. This regimen is currently tested prospectively within an ongoing international trial against 3 cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176). Clinical trial information: EudraCT 2004-003979-36.