Dietary modification is a cornerstone of cardiovascular disease (CVD) prevention. A Mediterranean diet has been associated with a lower risk of CVD but no systematic reviews have evaluated this relationship specifically in women. To determine the association between higher versus lower adherence to a Mediterranean diet and incident CVD and total mortality in women. A systematic search of Medline, Embase, CINAHL, Scopus, and Web of Science (2003-21) was performed. Randomised controlled trials and prospective cohort studies with participants without previous CVD were included. Studies were eligible if they reported a Mediterranean diet score and comprised either all female participants or stratified outcomes by sex. The primary outcome was CVD and/or total mortality. A random effects meta-analysis was conducted to calculate pooled hazard ratios (HRs) and confidence intervals (CIs). Sixteen prospective cohort studies were included in the meta-analysis (n=7 22 495 female participants). In women, higher adherence to a Mediterranean diet was associated with a lower CVD incidence (HR 0.76, 95% CI 0.72 to 0.81; I2=39%, p test for heterogeneity=0.07), total mortality (HR 0.77, 95% CI 0.74 to 0.80; I2=21%, p test for heterogeneity=0.28), and coronary heart disease (HR 0.75, 95% CI 0.65 to 0.87; I2=21%, p test for heterogeneity=0.28). Stroke incidence was lower in women with higher Mediterranean diet adherence (HR 0.87, 95% CI 0.76 to 1.01; I2=0%, p test for heterogeneity=0.89), but this result was not statistically significant. This study supports a beneficial effect of the Mediterranean diet on primary prevention of CVD and death in women, and is an important step in enabling sex specific guidelines. © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.