Background <p>Integrated occupational safety and health and patient safety management are essential for addressing the challenges faced by healthcare services today. Developing and evaluating tools that support this work is crucial. This project aims to assess the effectiveness of a structured method for systematic and integrated occupational safety and health and patient safety management systems (SIOHPS). Additionally, the project includes embedded economic and process evaluation. This article presents the overall design of the SIOHPS-project, with a specific focus on the design and evaluation of the (cost-)effectiveness study.</p> Methods <p>The project is guided by the Medical Research Council (MRC) framework for complex interventions and is coproduced with key stakeholders. The intervention is designed to support systematic occupational health and patient safety management systems, incorporating both Safety I and Safety II perspectives. It is grounded in safety culture theory and knowledge about team debriefing for learning. The intervention consists of several core components, including targeted education, end-of-shift team debriefings, and support for systematic management. The intervention is supported by a digital tool. A program theory guides the evaluation. A pragmatic stepped-wedge cluster-controlled design (p-SWD) is used, with hospital healthcare units as clusters. The p-SWD includes three steps, with at least four clusters transitioning from the control to the intervention group at each step. A minimum of twelve healthcare units from two different regions in Sweden will participate. The intervention effect will be evaluated using sick leave and quality of care as primary outcomes. Secondary outcomes include safety climate, work environment factors, healthcare worker health, performance, patient safety and quality of nursing care. Primary and secondary analyses are conducted based on intention-to-treat approach. Cost-effectiveness will be assessed using cost-benefit and cost-consequence analyses.</p> Discussion <p>The need of methods that integrate systematic occupational safety and health and patient safety management has been emphasized by different stakeholders worldwide. The SIOHPS study has strong potential for nationwide implementation in Sweden to help healthcare organizations address current challenges. Additionally, the project will contribute to existing safety culture theory by exploring the integration of these domains.</p> Trial registration <p>ClinicalTrials.gov Identifier: NCT06398860. Registration date: 2024-04-30.</p>