Purpose: The purpose of this study was to evaluate 18F-FLT PET/CT as an early prognostic imaging biomarker of long-term overall survival (OS) and disease-specific survival (DSS) in soft tissue sarcoma (STS) patients treated with neoadjuvant therapy (NAT) and surgical resection. Methods: This is a 10-year follow up of a previous, single-center, single-arm, prospective clinical trial. Patients underwent 18F-FLT PET/CT prior to treatment (PET1) and after NAT (PET2). Post-treatment pathology specimens were assessed for tumor necrosis / fibrosis as well as Ki-67 and TK1 expression. Maximally selected cut-offs for PET and histopathologic factors were applied. Survival was calculated from the date of subject consent to the date of death or last follow-up. Results: The study population consisted of 26 patients who underwent PET1, 16/26 primary STS underwent PET2. Thirteen deaths occurred during a median follow up period of 104 months. In the overall cohort, OS was longer in patients with low versus high PET1 tumor SUVmax (dichotomized by SUVmax ≥ 8.5 vs. < 8.5; not yet reached vs. 49.7 months; P = 0.0064). DSS showed a trend toward significance (P = 0.096). In a sub-analysis of primary STS, DSS was significantly longer in patients with low versus high PET1 tumor SUVmax (dichotomized by SUVmax ≥ 8 vs < 8; P = 0.0034). There were no significant 18F-FLT PET response thresholds corresponding to DSS or OS following NAT at PET2. Conclusion: 18F-FLT PET may serve as prognostic baseline imaging biomarker for DSS in patients with primary STS. Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.