Background: Associations between tumor metabolic and volumetric parameters determined by preoperative F-18-fluorodeoxyglucose-positron emission tomography and survival in patients with esophageal squamous cell carcinoma who underwent trimodal therapy have not been fully investigated. Methods: We evaluated relationships between reductions in maximal standardized uptake value, metabolic tumor volume, and total lesion glycolysis in primary tumors on F-18-fluorodeoxyglucose -positron emission tomography images between before and after neoadjuvant chemoradiotherapy and the survival of 120 patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy followed by surgery. Results: The optimal cutoffs of Delta maximal standardized uptake value, Delta metabolic tumor volume, and Delta total lesion glycolysis were defined to statistically yield the largest differences in recurrence-free survival for good and poor positron emission tomography responders to neoadjuvant chemoradiotherapy (cutoffs: 70%, 85%, and 90%, respectively). These cutoff values significantly stratified overall survival (Delta maximal standardized uptake value, P = .004; Delta metabolic tumor volume, P = .001; Delta total lesion glycolysis, P < .0001). Univariate analysis showed that Delta maximal standardized uptake value (hazard ratio, 0.50; 95% confidence interval, 0.32-0.79; P = .003), Delta metabolic tumor volume (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P = .004), and Delta total lesion glycolysis (hazard ratio, 0.37; 95% confidence interval, 0.23-0.61; P < .001) were statistically significant for recurrence-free survival. Furthermore, Delta metabolic tumor volume (hazard ratio, 0.45; 95% confidence interval, 0.27-0.76; P = .003) and Delta total lesion glycolysis (hazard ratio, 0.37; 95% confidence interval, 0.22-0.63; P < .001) were independent factors for recurrence-free survival in multivariate analyses that included preoperative and pathological factors. Conclusion: Together with significant pathological prognostic factors, Delta metabolic tumor volume and Delta total lesion glycolysis were valuable for patients with esophageal squamous cell carcinoma who received trimodal therapy. Thus, preoperative F-18-fluorodeoxyglucose-positron emission tomography is a useful and noninvasive diagnostic tool that might facilitate tailoring optimal therapies for locally advanced esophageal squamous cell carcinoma. (C) 2022 Elsevier Inc. All rights reserved.