: Low-molecular-weight heparin (LMWH) is the anticoagulant drug class of choice for the prevention of thrombosis during pregnancy and often used for prevention of severe obstetrical complications, yet the optimal dosage is still a matter of debate. Although several studies have evaluated LMWH dose adjustment methods based on anti-Xa levels, no definitive conclusion as yet exists. This extensive retrospective study sought to address the rationale of regular anti-Xa activity monitoring in pregnant patients given LMWH prophylaxis. We evaluated pregnant patients receiving LMWH prophylaxis with three or more anti-Xa measurements. The initial LMWH dose was fixed and adjusted for obesity. The desired anti-Xa activity was 0.2-0.6 IU/ml and LMWH dose was increased for anti-Xa levels less than 0.3 IU/ml. Of the 173 enrolled women, 79% required LMWH dose adjustment (56%: one dose increase; 20%: two; 3%: three). In the vast majority of patients, LMWH dose was increased before substantial body weight gain. The number of dose adjustments positively correlated with BMI, though not with body weight gain. Based on our study findings, we recommend conducting LMWH dose adjustments based on anti-Xa levels, monitored regularly during pregnancy to keep the anti-Xa activity within the desired range.