Conflicting evidence surrounds the effect of dietary macronutrient intake (fat, carbohydrate and protein) on cardiovascular disease (CVD), particularly in women. Women (aged 50-55 years) were recruited into the Australian Longitudinal Study on Women's Health. Women were divided into quintiles according to their carbohydrate and saturated fat intake as a percentage of total energy intake (TEI). The primary endpoint was new-onset CVD (heart disease/stroke). Secondary endpoints included all-cause mortality, incident hypertension, obesity and/or diabetes mellitus. Multivariate logistic regression models assessed for associations with the primary and secondary endpoints, with adjustment for confounders. A total of 9899 women (mean age 52.5±1.5 years) were followed for 15 years, with 1199 incident CVD and 470 deaths. On multivariable analysis, higher carbohydrate intake was associated with lower CVD risk (ptrend<0.01), with the lowest CVD risk for quintile 3 (41.0%-44.3% energy as carbohydrate) versus quintile 1 (<37.1% energy as carbohydrate) (OR 0.56, 95% CI 0.35 to 0.91, p=0.02). There was no significant association between carbohydrate intake and mortality (ptrend=0.69) or between saturated fat intake and CVD (ptrend=0.29) or mortality (ptrend=0.25). Both increasing saturated fat and carbohydrate intake were significantly inversely associated with hypertension, diabetes mellitus and obesity (ptrend<0.01 for all). In middle-aged Australian women, moderate carbohydrate intake (41.0%-44.3% of TEI) was associated with the lowest risk of CVD, without an effect on total mortality. Increasing saturated fat intake was not associated with CVD or mortality and instead correlated with lower rates of diabetes, hypertension and obesity. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.