ABSTRACT: Background: Sex-based disparities in the presentation, management, and outcomes of infective endocarditis (IE) remain insufficiently characterized despite their growing recognition. This study systematically evaluates current evidence on sex differences in the presentation, treatment, and outcomes of IE. Methods: A systematic review and meta-analysis were conducted according to PRISMA and Cochrane guidelines. EMBASE, MEDLINE, PubMed, the Cochrane Library, and Google Scholar were searched up to October 2024. Twenty-four studies including 139,952 patients (79,698 men and 60,254 women) were analyzed. Primary outcomes were mortality (in-hospital, 30-day, and 1-year), stroke, and treatment modality (medical vs. surgical). Secondary outcomes included complications, procedural characteristics, and hospital course. Results: Men were younger at diagnosis and had higher rates of substance abuse and coronary artery disease, while women more often had hypertension, diabetes, chronic lung disease, and prior valvular pathology. Men more frequently had aortic and prosthetic valve IE, whereas women had mitral and tricuspid involvement. Men were about 65% more likely to undergo surgery for infective endocarditis than women, while women were predominantly managed medically. Men had lower in-hospital (OR 0.81, 95% CI 0.72-0.92) and 1-year mortality (OR 0.76, 95% CI 0.61-0.94), though 30-day mortality did not differ significantly. Women experienced shorter hospital stays but longer ICU admissions and more heart failure, whereas men had more recurrent IE. Conclusions: Men underwent surgery more often and had better short- and long-term survival. Women presented later, with greater comorbidity and higher complication rates. Enhanced recognition of sex-specific risk and equitable surgical referral may improve IE outcomes.