For couples with sickle cell trait (SCT) who are at risk for having a child with sickle cell disease (SCD), cost is a barrier to using in vitro fertilization (IVF) with preimplantation genetic testing for monogenic diseases (PGT-M) and insurance coverage is not universal. The objective of this study was to evaluate the cost-effectiveness of IVF+PGT-M for couples who both carry SCT and wish to avoid SCD in a child compared to natural conception with the possible birth of a child with SCD, and the associated lifetime medical costs and lost income. A cost-effectiveness analysis was performed with a decision analytic model. Sensitivity analyses, including Monte Carlo Simulations, assessed the impact of changes in input parameters on the incremental cost-effectiveness ratio (ICER). Probabilities and cost estimates were derived from the published literature. Effectiveness was measured in life years (LY) gained. The ICER was calculated to determine the cost-effectiveness of the IVF+PGT-M intervention. Compared to natural conception, IVF+PGT-M had an effectiveness gain of 30 LY, an additional cost of $572,392.68 per individual conceived, and an ICER of $19,319 per LY gained. The ICER is lower than a conservative, preset willingness to pay (WTP) threshold of $50,000 per LY gained. Monte Carlo Simulations demonstrated that, in 91% of iterations, IVF+PGT-M was cost-effective at the WTP of $50,000. IVF+PGT-M is a cost-effective strategy to avoid conceiving a child with SCD and broader insurance coverage is warranted. This article is protected by copyright. All rights reserved.