Objective—To evaluate if the association between prenatal care use and birth weight (BW) varies for infants with cleft lip and/or cleft palate (CL/P), classified into isolated and non-isolated forms, compared with unaffected infants. Study design—The study employed two datasets. The first included a multi-country sample of 2,405 infants with CL/P and 24,046 infants without CL/P born in 1996–2007 in South America. The second was a sample of 2,122 infants with CL/P and 297,415 without CL/P from the United States (U.S.) 2004 Natality dataset. Separate analyses were performed for the South American and U.S. samples. The association between prenatal care and BW was evaluated separately for isolated CL/P, non-isolated CL/P, and unaffected infants using regression models adjusting for several background characteristics. Results—Prenatal care was associated with improved BW for all infant groups, with greater BW increases for infants with CL/P particularly non-isolated forms. In the South American sample, BW increased by 108, 69, and 40 grams on average per prenatal visit for infants with non-isolated CL/P, infants with isolated CL/P, and unaffected infants, respectively. In the U.S. sample, BW increased by 51, 21, and 16 grams on average per prenatal visit for these infant groups, respectively. Conclusions—Prenatal care was associated with larger BW increases for pregnancies complicated with CL/P, particularly non-isolated forms, compared with unaffected pregnancies. Given that reduced BW is a well-recognized co-morbidity of CL/P, the findings highlight the importance of prenatal care for at-risk pregnancies as a tertiary-prevention intervention to reduce the health burden of CL/P.