Background Distal radius fractures are the most frequently encountered fractures in Western societies, typically affecting patients aged 50 years and older. Although this is a common injury, the best treatment for these fractures in older patients is still under debate. Objective This prospective study aims to compare the outcome of operatively and nonoperatively treated distal radius fractures in the older population. Only patients with distal radius fractures for which equipoise regarding the optimal treatment exists will be included. Methods This prospective international multicenter observational cohort study will be designed as a natural experiment. Natural experiments are observational studies in which treatment allocation is determined by factors outside the control of the investigators but also (largely) independent of patient characteristics. Patients aged 65 years and older with an acute distal radius fracture will be considered for inclusion. Treatment allocation (operative vs nonoperative) will be based on the local preferences of the treating hospital either in Switzerland or the Netherlands. Hence, the process governing treatment allocation resembles that of randomization. Patients will be identified after treatment has been initiated. Based on the radiographs and baseline information of the patient, an expert panel of 6 certified trauma surgeons from 2 regions will provide their treatment recommendation. Only patients for whom the experts disagree on treatment recommendations will ultimately be included in the study (ie, for whom there is a clinical equipoise). For these patients, both operative and nonoperative treatment of distal radius fractures are viable, and treatment choice is predominantly determined by personal or local preference. The primary outcome will be the Patient-Rated Wrist Evaluation score at 12 weeks. Secondary outcomes will include the Physical Activity Score for the Elderly, the EQ questionnaire, pain, the living situation, range of motion, complications, and radiological outcomes. By including outcomes such as living situation and the Physical Activity Score for the Elderly, which are not relevant for younger cohorts, valuable information to tailor treatment to the needs of the older population can be gained. According to the sample size collection, which was based on the minimal important clinical difference of the Patient-Rated Wrist Evaluation, 92 patients will have to be included, with at least 46 patients in each treatment group. Results Enrollment began in July 2023 and is expected to continue until summer 2024. The final follow-up will be 2 years after the last patient is included. Conclusions Although many trials on this topic have previously been published, there remains an ongoing debate regarding the optimal treatment for distal radius fractures in older patients. This observational study, which will use a fairly new methodological study design, will provide further information on treatment outcomes for older patients with distal radius fractures for which to date equipoise exists regarding the optimal treatment. International Registered Report Identifier (IRRID) DERR1-10.2196/52917