Mechanical prosthetic heart valves (MPHVs) are highly thrombogenic, and a pregnancy-induced procoagulant status increases the risk of MPHV thrombosis. Despite numerous case reports, 2 major registries and meta-analyses/systematic reviews, optimal anticoagulation therapy during pregnancy remains controversial. The goal of this study was to evaluate different anticoagulation regimens in pregnant patients with MPHVs. The outcomes of anticoagulation regimens were assessed retrospectively in pregnant women (110 women; 155 pregnancies) with MPHVs. The study population was divided into 5 groups according to anticoagulation regimens used; high-dose warfarin (>5 mg/d) throughout pregnancy (group 1), low-dose warfarin (≤5 mg/d) throughout pregnancy (group 2), low molecular weight heparin (LMWH) throughout pregnancy (group 3), first trimester LMWH, 2nd and 3rd trimester warfarin (group 4), first 2 trimester LMWH, and 3rd trimester warfarin (group 5). Of 155 pregnancies, 55 (35%) resulted in fetal loss; whereas 41 (27%) cases with abortion (miscarriage and therapeutic) and 14 (9%) stillbirths occurred. The comparison of the groups showed that the whole abortion rates including therapeutic abortion were significantly higher in Group 1, and lower in groups 3 and 5 (p <0.001). However, miscarriage rates were similar between the groups. A total of 53 pregnancies (34%) suffered from prosthetic valves thrombosis (PVT) during pregnancy or in the postpartum period. Group 2 had significantly lower rates of PVT than the other groups (p <0.001). In conclusion, the current data suggests that there is no optimal therapy, and that all managements have advantages and disadvantages. Low-dose warfarin (≤5 mg/day) regimen with therapeutic international normalized ratio levels may provide effective maternal protection throughout pregnancy with acceptable fetal outcomes.