Objective: To assess change in health and well-being using generic and disease-specific self-report instruments among patients with diabetes-related foot ulcers (DFU) receiving a telemedicine intervention compared to patients receiving standard hospital outpatient care. Research Design and Methods: This cluster randomized controlled trial (RCT) included 182 adults with DFU (94/88 in the telemedicine/standard care groups) in 42 municipalities/districts, recruited from three clinical sites in Western Norway. The main purpose of the trial was to evaluate whether ulcer healing time in the telemedicine intervention was non-inferior to standard outpatient care. The intervention group received care in the community in collaboration with specialist health care via telemedicine; the control group received standard care. In the current study secondary endpoints as health and well-being were evaluated by four generic health and well-being questionnaires (e.g., WHO-5, EQ-5D) and two disease-specific questionnaires (Neuro-QoL, PAID). We used linear mixed-effects regression to investigate differences in change in the sum scores between the intervention and control group at the end of follow-up. Results are reported as regression coefficients with 95% CIs. Results: In intention to treat analyses, differences between treatment groups were small and non-significant for the generic health and well-being scale scores, as well as for diabetes-related distress and foot ulcer-specific quality of life. Conclusion: This is the first RCT assessing the effect of a telemedicine diabetic foot ulcer intervention on health and well-being. There were no significant differences in change in sum scores for health and well-being between the intervention and control group. TM was non-inferior to SOC regarding healing time. Further studies are needed to investigate long-term intervention effects on new or recurrent foot ulcers and corresponding health and well-being. Disclosure M.M. Iversen: None. J. Igland: None. H. Smith-Strøm: None. T. Ostbye: None. G.S. Tell: None. S. Skeie: None. J.G. Cooper: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Speaker's Bureau; Self; Novo Nordisk A/S. M. Graue: None. Funding Norwegian Directorate of Health and Innovation; Western Norway Regional Health Authority (911716, 911605); Norwegian Diabetes Association; Western Norway University of Applied Sciences; Norwegian Research Council (221065)