Introduction: Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. Objective: To assess the relationship between maternal smoking, gender and CL/P. Methods: This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: Cases: mothers of children with CL/P (n = 843) and Controls: mothers of children without CL/P (n = 676). All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. Results: An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR = 3.51; 95% CI 2.83-4.37). By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. Conclusion: Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential. © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial Ver menos