Hepatitis C virus (HCV) epidemiology has shifted from the baby-boomer generation to young women of childbearing age. The health benefits and cost-effectiveness (CE) of screening pregnant women remain controversial. To systematically review published studies evaluating the CE of screening pregnant women for HCV in the era of direct-acting antivirals (DAAs). We conducted a systematic literature search of CE studies evaluating the costs and benefits of screening pregnant women for HCV. Pertinent information including antiviral agent, drug costs, incremental cost-effective ratio (ICER), and infant care was collected. The authors' definition of the threshold price at which screening was deemed CE was also recorded. The quality of studies was assessed using the Consolidated Health Economic Evaluation Reports Standards (CHEERS) checklist. We identified 5 studies that evaluated the ICER of screening pregnant women for HCV. Of these, 2 utilized all oral DAAs, with universal screening CE. The ICER of these 2 studies was $3000 and $41,000 per quality of life-years gained. The remaining studies were interferon-based regimens. Most studies did not include screening of infants. Universally screening pregnant women for HCV was CE in studies that utilized oral DAAs. Most pharmacoeconomic studies failed to incorporate the impact of vertical transmission on infants.