We carried out this study to compare the effect of consuming whole, partially defatted and defatted cows’ milk for 4 months on serum concentrations of blood indicators of cardiovascular risk (CVR) in Mexican children and adolescents. Children aged between 6 and 16 years living in indigenous boarding schools in Mexico and who were usual consumers of whole milk were recruited to this study. Totally, thirteen boarding schools were randomly selected to receive full supplies of whole, partially defatted and defatted cows’ milk for 4 months. Serum total cholesterol (TC), TAG, HDL-cholesterol, apoA and total apoB, and Lp(a) concentrations were measured before and after the intervention. Comparisons were made with multi-level mixed-effects linear regression models using the difference in differences approach. Compared with the whole milk group, TC, LDL-cholesterol, HDL-cholesterol and total apoB were lower in defatted milk consumers by –0·43, –0·28, –0·16 mmol/l and −0·05 g/l, respectively (all P<0·001). Compared with the whole milk group, the group that consumed partially defatted milk showed a significant decrease in the concentrations of LDL-cholesterol (−0·12, P=0·01), apoA (−0·05 g/l, P=0·01) and total apoB (−0·05 g/l, P=0·001). Defatted milk intake for 4 months reduced some of the serum indicators of CVR.