BACKGROUND: Preimplantation testing for structural rearrangements (PGT-SR) is used to screen embryos for chromosomal imbalances that may result from parental structural rearrangements. We conducted a health technology assessment of PGT-SR for carriers of structural rearrangements or people who may have a child with a genetic condition affected by structural rearrangements, which included an evaluation of effectiveness. A report describing a rapid review of the qualitative literature, direct patient engagement, a review of published literature examining ethical considerations relating to PGT, and a rapid review of the obstetrical and neonatal harms of PGT using trophectoderm biopsy has been published separately. METHODS: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias Assessment Tool for Nonrandomized Studies version 2 (RoBANS 2) and the quality of the body of evidence according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. RESULTS: We included 4 studies in the clinical evidence review. Compared with in vitro fertilization (IVF) without PGT-SR, PGT-SR may result in similar live birth rates (first transfer and cumulative) (GRADE: Very low), pregnancy rate (clinical and ongoing) (GRADE: Very low), and spontaneous pregnancy loss (GRADE: Very low). Compared with natural conception or expectant clinical management, PGT-SR may result in similar live birth rates (first transfer and cumulative) and time to pregnancy, reduced spontaneous pregnancy loss (GRADE: Very low), and increased multiple gestation pregnancy (GRADE: Very low). CONCLUSIONS: PGT-SR may result in similar outcomes compared with IVF without PGT-SR, may reduce spontaneous pregnancy loss compared with natural conception, and may increase multiple gestation compared with natural conception, although the evidence is very uncertain.