Abstract Aim To evaluate a deep learning-based time-of-flight (DLToF) model trained to enhance the image quality of non-ToF PET images for different tracers, reconstructed using BSREM algorithm, towards ToF images. Methods A 3D residual U-NET model was trained using 8 different tracers (FDG: 75% and non-FDG: 25%) from 11 sites from US, Europe and Asia. A total of 309 training and 33 validation datasets scanned on GE Discovery MI (DMI) ToF scanners were used for development of DLToF models of three strengths: low (L), medium (M) and high (H). The training and validation pairs consisted of target ToF and input non-ToF BSREM reconstructions using site-preferred regularisation parameters (beta values). The contrast and noise properties of each model were defined by adjusting the beta value of target ToF images. A total of 60 DMI datasets, consisting of a set of 4 tracers (18F-FDG, 18F-PSMA, 68Ga-PSMA, 68Ga-DOTATATE) and 15 exams each, were collected for testing and quantitative analysis of the models based on standardized uptake value (SUV) in regions of interest (ROI) placed in lesions, lungs and liver. Each dataset includes 5 image series: ToF and non-ToF BSREM and three DLToF images. The image series (300 in total) were blind scored on a 5-point Likert score by 4 readers based on lesion detectability, diagnostic confidence, and image noise/quality. Results In lesion SUVmax quantification with respect to ToF BSREM, DLToF-H achieved the best results among the three models by reducing the non-ToF BSREM errors from -39% to -6% for 18F-FDG (38 lesions); from -42% to -7% for 18F-PSMA (35 lesions); from -34% to -4% for 68Ga-PSMA (23 lesions) and from -34% to -12% for 68Ga-DOTATATE (32 lesions). Quantification results in liver and lung also showed ToF-like performance of DLToF models. Clinical reader resulted showed that DLToF-H results in an improved lesion detectability on average for all four radiotracers whereas DLToF-L achieved the highest scores for image quality (noise level). The results of DLToF-M however showed that this model results in the best trade-off between lesion detection and noise level and hence achieved the highest score for diagnostic confidence on average for all radiotracers. Conclusion This study demonstrated that the DLToF models are suitable for both FDG and non-FDG tracers and could be utilized for digital BGO PET/CT scanners to provide an image quality and lesion detectability comparable and close to ToF.