Aim - the purpose of the study is the development of a method for prevention of pathological pregnancy syndrome from the perspective of integral genesis, determined by morphological and functional abnormalities in the fetoplacental system, assessing the effectiveness of methodological standards of evidence-based medicine. Materials and methods. Prospective study of 435 women with high risk of decompensation of placental insufficiency was conducted. Depending on the method of prevention of gestational complications 4 groups were formed: 1st group included 145 pregnant women, who were prescribed dydrogesterone on the 6-20 weeks of gestation, and starting with the 21st week - highly-purified diosmin 600 mg as vasoprotective; in the 2nd group 118 women received a course of preventive treatment with low doses of acetylsalicylic acid; 3rd group included 102 patients who underwent a course of preventive monotherapy with magnesium; 4th group comprised 70 pregnant women who refused preventive treatment. A control group encompassed 30 healthy pregnant women. Dynamic survey included definition of markers of endothelial and hemostasiological dysfunction, vascular-platelet dysfunction elements, apoptosis, inflammatory response, total reactive capacity of the organism, magnesium and carbon dioxide concentrations; a hystostereometric study of placenta was conducted. Standards of evidence-based medicine were applied for the objectification of the effectiveness of the developed method. Results. Method of preventing great obstetric syndromes by successive appointment of progestogen dydrogesterone on the early stage of pregnancy followed by vasoprotective diosmin 600 mg in the 2nd half of pregnancy showed high efficiency (NNT 1.4 (95% CI 1.1 -1.7); OSH 5.3 (95% CI 4.7 -5.8), namely reducing pre-eclampsia by 93%, placental insufficiency with intrauterine growth restriction and/or chronic fetal hypoxia - 95%, preterm birth - 86%, and no premature abruption of normally situated placenta, severe forms of pre-eclampsia and placental insufficiency. Higher clinical effectiveness of the proposed method of prophylaxis of pathological pregnancy syndrome, compared to the use of low-dose acetylsalicylic acid and preparation of magnesium, can be explained by the normalizing effect of dydrogesterone and highly-purified diosmin 600 mg on the immune and biochemical homeostasis, apoptosis and angiogenesis, activation of endothelial and hemostasiological system, adaptive compensatory reactions in the placenta. Conclusion. The method of choice for the prevention of pathological pregnancy syndrome at high risk of fetoplacental system decompensation is the application of progestogen dydrogesterone and vasoprotective diosmin according to the developed method. The study revealed the potential of targeted selection of preventive methods depending on special needs of pregnant women.