INTRODUCTION: Infective endocarditis is a rare but severe disease affecting 3-10 per 100 000 each year associated with a mortality of 25%. However, it is thought to affect females more severely than men, despite lower incidence. However, reasons for this are unknown, and there is controversy surrounding evidence for differences in surgical outcomes for infective endocarditis. Thus, a systematic review and meta-analysis is warranted to elucidate differences in outcomes by gender. METHODS AND ANALYSIS: This systematic review protocol has been developed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic search including synonyms of the terms 'infective endocarditis', 'cardiac surgery' and 'sex', was carried on MEDLINE, Embase and Scopus databases (full search available in the Supplementary Material) to identify relevant studies. The Cochrane Risk of Bias 2 tool and Newcastle-Ottawa Scale will be used to assess the quality of the available studies and risk of bias. Studies will be screened using predetermined inclusion and exclusion criteria. Data will be summarized narratively and in tabular forms. A pairwise meta-analysis will be carried out with a random effects model to examine differences in mortality and postoperative complications between males and females. DISCUSSION: The findings will elucidate the influence of gender on surgical outcomes for infective endocarditis, informing evidence-based interventions and emphasizing the need for equitable surgical care. By identifying risk factors specific to women, this study aims to improve management strategies and outcomes for female patients with infective endocarditis. Results will be disseminated via peer-reviewed publications and relevant conferences.