Soya protein has well-documented beneficial effects on serum lipid levels in adults, the potential beneficial effect of a prolonged soya protein-substituted diet in children and adolescents with familial (FH) and polygenic hypercholesterolaemia (PH) being unknown. To assess the effect of 3 months’ treatment of children and adolescents with FH and PH with a soya-substituted diet on serum lipids and lipoproteins, twenty-three children and adolescents were initially assigned to a standard phase 1 diet for 3 months, after which they were instructed to include soya protein (0·25–0·5 g/kg body weight) into their diet for 3 months. Sixteen patients (ten males and six females, thirteen with FH (eight males and five females), three with PH (two males and one female); mean age 8·8 (sd 4·2) years (range 4–18 years); mean BMI 16·7 (sd 2·6) kg/m2)) completed both phases. The phase 1 diet resulted in a significant reduction of total cholesterol (TC), LDL-cholesterol and apo B by 12·3, 11·8 and 10·6 %, respectively, HDL-cholesterol, TAG, apo A1 and lipoprotein(a) not being different. Dietary intake of soya protein during phase 2 resulted in a significant decrease of TC, LDL-cholesterol and apo B by 7·7, 6·4, and 12·6 %, respectively. TAG, HDL-cholesterol, apo A1, and lipoprotein(a) did not change significantly. Substitution of soya protein for animal protein in a low-fat, fat-modified diet is of additional benefit in many, but not all, children and adolescents with FH and PH when aiming at lowering serum TC, LDL and apo B. It seems to be a feasible long-term dietary lifestyle intervention and may grant additive benefit in the prevention of early vascular disease.