Background: To determine whether high-risk STS patients identified using individual patient data and the nomogram Sarculator, benefitted from adjuvant chemotherapy in a RCT which failed to detect any overall survival (OS) differences between chemotherapy and observation. Methods: Data from the EORTC 62931 RCT comparing adjuvant doxorubicin plus ifosfamide (Adj) and observation (Obs) for STS (Lancet Oncol 2012;13:1045-1054) were analysed. 10-yr predicted probability of OS (P-OS) was computed using a validated nomogram (Lancet Oncol 2016;17:671-80) for each participant with extremity and trunk wall STS (N = 290/351). Patients were divided in 3 categories of P-OS. OS and disease-free survival (DFS) were calculated at the study median follow-up (8-yr). Results: Nomogram P-OS were dispersed (median 72%, IQR 57-83%) and had prognostic value for OS and DFS (Log-Rank test: P < 0.001). Patients were grouped in 3 arbitrary P-OS categories: > 66% (high P-OS), > 51≤ 66 (intermediate P-OS), ≤ 51% (low P-OS). Most patients were in the high P-OS category (N = 170 [58.6%], 90 Obs/80 Adj), while 68 (23.5%, 34 Obs/34 Adj) and 52 (17.9%, 24 Obs/28 Adj) fell in the intermediate and low P-OS category, respectively. Adjuvant chemotherapy halved the risk of death in patients with low P-OS (HR = 0.46, 95%CI 0.23-0.94) with a 21.2% 8-yr absolute risk reduction (ARR) of death (8-yr OS: 42% and 21% for Adj and Obs, respectively). This effect was not detected in the intermediate (HR = 1.00, 95%CI 0.53-1.88) and high P-OS categories (HR = 1.08, 95%CI 0.61-1.90). There was a DFS benefit for chemotherapy in low P-OS (HR = 0.46, 95%CI 0.24-0.89) but not in the intermediate (HR = 0.74, 95%CI 0.41-1.34) and high P-OS (HR = 0.90, 95%CI 0.54-1.50) categories, leading to a 21% 8-yr ARR for adjuvant chemotherapy (8-yr DFS: 34% and 13% for Adj and Obs, respectively). Conclusions: In this RCT patients with a low predicted P-OS (i.e., high-risk patients) have a statistically significant higher OS and DFS when treated with the study doxorubicin-ifosfamide chemotherapy, although the analysis on all study patients was negative. Clinical trial information: NCT00002641