Objective : To evaluate the association of the polymorphisms in the TGFB3 gene (rs2268626) and the BMP4 gene (rs17563) with nonsyndromic oral clefts. Design : A hospital-based case-control study was conducted with nonsyndromic oral clefts cases and unaffected controls. Cleft type and tooth agenesis data were collected by clinical examination and confirmed through medical records. Risk factors were obtained through a questionnaire. Genotyping of the selected polymorphisms for TGFB3 and BMP4 were carried out by real-time polymerase chain reaction using the Taqman assay method from a genomic DNA isolated from buccal epithelial cells of all individuals. Setting : The case group was ascertained through a public reference hospital of oral cleft rehabilitation in Rio de Janeiro, Brazil. The noncleft group consisted of unrelated subjects, with no history of oral cleft in the family, recruited at the Dental Clinic at the Federal University of Rio de Janeiro, Brazil. Participants : A total of 833 unrelated individuals (450 control individuals and 383 cases with nonsyndromic oral clefts). Results : No significant association in relation to genotype or allele distributions for TGFB3 polymorphism was found between oral cleft subgroups and the control group. For BMP4, there were significant differences in the genotype frequencies between the oral cleft and control groups (P = .0007). Regarding cleft type, there were statistically significant differences between the cleft lip and control groups (P = .00009). Conclusion : Our findings provide preliminary evidence suggesting that the risk of nonsyndromic oral clefts may be influenced by variation in the BMP4 gene.