The prothrombin G20210A factor II mutation carrier status has been reported to cause complications during pregnancy. This report presents the case of a patient diagnosed with heterozygous prothrombin G20210A factor II mutation at 29 years of age during preconception genetic screening. The patient had two uncomplicated pregnancies. The patient underwent laparoscopic cholecystectomy with a complicated postoperative course. The complications included deep vein thrombophlebitis (DVT), portal vein thrombosis (PVT), and pulmonary embolization (PE). The treatment options and contraceptive choices are also discussed in this report. Our report discusses the subsequent risks inherent in a heterozygote following the administration of oral contraceptives, prolonged immobilization related to lower extremity trauma, and extended motor vehicle excursion.