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Background and objectives Cardiovascular diseases, particularly those involving valvular and coronary conditions, lead to significant global mortality. Current strategies combine surgeries like valve replacement and coronary artery bypass grafting, which can increase perioperative risks. Research indicates that physiology-guided strategies such as fractional flow reserve and quantitative flow ratio improve outcomes by guiding more precise surgical interventions. This study aims to compare physiology-guided and angiography-guided surgical strategies, focusing on evaluating their efficacy and safety in treating patients with combined valvular and coronary pathologies.Methods and analysis We will search PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform for studies comparing outcomes of physiology-guided and angiography-guided strategies for patients with valvular diseases combined with coronary heart disease. All English articles published before 31 May 2024 will be considered. The primary outcomes will be major adverse cardiovascular events and graft occlusion rate. The secondary outcomes will be cardiac death, myocardial infarction, stroke, repeat revascularisation, and so on. The Jadad score and Newcastle-Ottawa Scale will be used to assess the quality of randomised controlled trials (RCTs) and non-RCTs, respectively. The Q-test and I² statistic will be used to assess the heterogeneity. For the primary outcome, we will perform the subgroup analysis if sufficient studies are available. We will also conduct leave-one-out sensitivity analysis to assess the impact of each individual study on the overall results. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines.Ethics and dissemination This study is a secondary analysis of previous studies and therefore does not require ethical approval. Our research will be disseminated in peer-reviewed publications.PROSPERO registration number CRD42024542876.