Disturbances of fasting and postprandial lipid profiles are major cardiovascular (CV) risk factors. Nutrition plays a key role in their modulation, notably in postmenopausal women at CV risk. Interest has grown on the potential benefits of milk polar lipids (MPL). However, effects of MPL supplementation in humans have been inconsistent, often due to trials being performed in healthy subjects by increasing lipid intake. We hypothesized that isolipidic enrichment of the diet with MPL via a realistic dairy product could improve lipid markers of CV risk. We notably targeted a 5-g/day dose using an originally designed butterserum microfiltration process (Gassi et al., Int. Dairy J., 2016). We performed a double-blind randomized controlled trial in 58 postmenopausal overweight women with HDL-cholesterol<1.5 mM. They were subjected to (i) a 4-week dietary intervention with daily consumption of a cream-cheese containing 12 g of milkfat randomly including either 0 g (control, n=19), 3 g (n=19) or 5 g (n=20) of MPL, and to (ii) 8h-postprandial explorations after a test meal, before and after intervention (i.e. 2 visits). Lipid markers were measured in plasma and in the chylomicron fraction. The effect of MPL dose was tested through a linear mixed model (SAS®). The 5 g MPL dose decreased fasting and postprandial total cholesterol (-0.33±0.03 mM, p<0.001) and plasma triglycerides (-0.35±0.05 mM, p<0.001), and decreased fasting total/HDL-cholesterol and ApoB/ApoA1 ratios (p<0.001) (effects different from control, p<0.05). The 5 g MPL dose decreased both chylomicron- cholesterol and -triglycerides (p<0.01), suggesting lower intestinal absorption and/or increased clearance. A pilot mechanistic study in ileostomized patients consuming the test cheeses including 2H-cholesterol tracer showed that MPL lowered intestinal cholesterol absorption. Altogether, our data suggest that a dietary strategy based on milk lipid quality, including MPL, can contribute to improve the cardiometabolic health of postmenopausal women.