The widespread adoption of electronic health records (EHR) provides a unique and novel opportunity to improve the efficiency of clinical research processes. The European EHR4CR (Electronic Health Records for Clinical Research) 4-year project has developed a technological platform to enable the reuse of EHR data for clinical research. The objective of this cost-benefit assessment (CBA) is to assess the value of EHR4CR solutions compared to current practices. Methods Three clinical research scenarios were selected: Protocol feasibility assessment (S1), patient identification for recruitment (S2), and clinical study conduct (S3). The approach considered that the estimated reduction in actual person-time and costs of performing EHR4CR S1, S2, S3 applied to a Phase II or Phase III oncology clinical trial as a reference case would accelerate time to market (TTM). Probabilistic sensitivity analyses were conducted. Results When converting the efficiency gains realized with the EHR4CR platform into potential financial value for achieving faster TTM, the absolute mean cost-benefit for the global pharmaceutical oncology sector was estimated at €161m (S1), €46m (S2), €1'904m (S3), €204m (S1+S2), and up to €2'119m (S1+S2+S3) when the three scenarios were used sequentially. Conclusions The results confirm that optimizing clinical trial design and study conduct with the EHR4CR platform would generate substantial added value for pharmaceutical industry. Disclosure The EHR4CR project is mandated by the Innovative Medicines Initiative (IMI) co-funded by the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA). Pharmaceutical innovation faces important research and development (R&D) challenges, including significant delays and escalating R&D costs. The average cost of developing a new drug is estimated at €1.2 billion 1. The average cost of clinical trials has increased threefold over the last 12 years 2 Clinical development process is lengthy and can last 8 to 10 years 3,4. Major R&D bottle necks include sub-optimal protocol designs, slow patient recruitment, and labor-intensive and time-consuming clinical study conduct. On average, there are 2-3 protocol amendments implemented per clinical trial. This number exceeds 3.5 for Phase III clinical trials 5. Each protocol amendment takes an average additional 61 days to implement and costs over USD450'000 3 Almost half of all trial delays are caused by participant recruitment problems 6. 48% of sites miss their enrollment targets in Phase II and III multi-center study 7. The percentages of studies that complete enrolment on time are 18 % in Europe, 17 % …