Background: Treatment of chronic diseases in the elderly with polypharmacy poses a threat to patient outcome and involves extensive costs. Little evidence exists regarding the benefits of polypharmacy, but rising evidence shows its harmful effects. Several approaches to reduce polypharmacy have been proposed, but none have been evaluated using clinically relevant endpoints.Aims: Based on a systematic review we will gather current best evidence and develop recommendations to optimize treatment of polymorbid elderly with cardiovascular disease, heart failure, hypertension, atrial fibrillation, diabetes mellitus type 2, musculoskeletal disorders, COPD, and mental diseases. We will then design an electronic decision support (eDS) tool incorporating the recommendations to be applied in primary care. The tool will be evaluated in a randomised controlled trial (RCT) to show that reduction of polypharmacy in the treatment of the target-diseases is beneficial and safe. Using the results of the RCT, the eDS-tool will be optimized and then disseminated for general utilization.Workplan: The project is scheduled for 4 years and will contain 12 work packages. WP1 comprises management of the project. The evidence regarding treatment of chronic diseases gathered within WP2 will be used to develop the eDS tool and an electronic case report form (eCRF) in WPs 3-4. After recruitment of surgeries and patients, and implementation of the tool in WP 5, the tool will be evaluated within a cluster-randomized controlled trial (WPs 6-10). The results of the RCT will be used to optimize the eDS tool (WP 11) which will then be disseminated (WP 12).Impact: The project will contribute to the EIP “Active and Healthy Ageing”. It will improve treatments suited to the needs of older people and lower health care costs by promoting standardized care and reducing hospital admissions. The tool will be exploited by one of the partners (Duodecim Medical Publications) to achieve widespread implementation