Abstract Aim To estimate the cost‐effectiveness of an intervention facilitating the early detection of adverse drug events through the means of health professional training and the application of a digital screening tool. Design Multi‐centred non‐randomized controlled trial from August 2018 to March 2020 including 65 nursing homes or home care providers. Methods We aim to estimate the effect of the intervention on the rate of adverse drug events as primary outcome through a quasi‐experimental empirical study design. As secondary outcomes, we use hospital admissions and falls. All outcomes will be measured on patient‐month level. Once the causal effect of the intervention is estimated, cost‐effectiveness will be calculated. For cost‐effectiveness, we include all patient costs observed by the German statutory health insurance. Results The results of this study will inform about the cost‐effectiveness of the optimized drug supply intervention and provide evidence for potential reimbursement within the German statutory health insurance system.