Background and purpose Few tools are available to predict tumor response to treatment. This retrospective study assesses visual and automatic heterogeneity from ¹⁸F-FDG PET images as predictors of response in locally advanced rectal cancer. Methods This study included 37 LARC patients who underwent an ¹⁸F-FDG PET before their neoadjuvant therapy. One expert segmented the tumor from the PET images. Blinded to the patient´s outcome, two experts established by consensus a visual score for tumor heterogeneity. Metabolic and texture parameters were extracted from the tumor area. Multivariate binary logistic regression with cross-validation was used to estimate the clinical relevance of these features. Area under the ROC Curve (AUC) of each model was evaluated. Histopathological tumor regression grade was the ground-truth. Results Standard metabolic parameters could discriminate 50.1% of responders (AUC = 0.685). Visual heterogeneity classification showed correct assessment of the response in 75.4% of the sample (AUC = 0.759). Automatic quantitative evaluation of heterogeneity achieved a similar predictive capacity (73.1%, AUC = 0.815). Conclusion A response prediction model in LARC based on tumor heterogeneity (assessed either visually or with automatic texture measurement) shows that texture features may complement the information provided by the metabolic parameters and increase prediction accuracy.