Women with polycystic ovary syndrome (PCOS), the most common endocrinopathy in reproductive age, are characterized by increased cardiometabolic risk. Similar hormonal and metabolic changes were found in their siblings. The purpose of our study was to compare blood pressure-lowering and pleiotropic effects of lisinopril between sisters of women with PCOS and their unrelated peers. The study included two age-, body mass index-, and blood pressure-matched groups of women with grade 1 hypertension: 26 sisters of PCOS probands (Group 1) and 26 individuals without a family history of PCOS (Group 2), receiving 10-40 mg of lisinopril daily. Blood pressure, glucose homeostasis markers, plasma levels of lipids (androgens, estradiol, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen, and uric acid), and urinary albumin-to-creatinine ratio (UACR) were measured before lisinopril treatment and 6 months later. At baseline, the study groups differed in insulin sensitivity, testosterone, free androgen index (FAI), hsCRP, homocysteine, and UACR. Blood pressure-lowering properties of lisinopril did not differ between the groups. The decrease in homocysteine and UACR, although observed in both groups, was stronger in Group 2 than in Group 1. Only in women without a family history of PCOS lisinopril improved insulin sensitivity and reduce hsCRP, fibrinogen, and uric acid. The remaining markers did not change throughout the study. Cardiometabolic effects of lisinopril correlated with testosterone, free androgen index, and changes in insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril may be slightly less pronounced in sisters of women with PCOS than in women without a family history of this disorder.