The objective of this study was to evaluate the impact of malocclusion on the quality of life (QOL) of adolescents in Brazil. We carried out a cross-sectional study in a sample population of 1015 schoolchildren aged 12 to 15 years from São Luís, Maranhão, Brazil. The explanatory variable was malocclusion, evaluated on the basis of the normative need or the adolescent's self-perceived need for dental treatment. Normative need for dental treatment was determined by professional diagnosis, made on the basis of Angle's classification, the Dental Aesthetic Index, and other morphological deviations (e.g., posterior crossbite, posterior open bite, and deep overbite). We analyzed the impact of malocclusion on the QOL using the Portuguese version of the Oral Health Impact Profile-14. Associations were estimated by using the prevalence ratio (PR) in Poisson regression analysis, with hierarchized modeling. An alpha of 5% was adopted as the criterion for statistical significance. The QOL of adolescents was impacted by malocclusion, classified by a normative need for treatment according to the Dental Aesthetic Index (PR = 1.27; 95% confidence interval [CI] = 1.03-1.56) or by the self-perceived need for treatment (PR = 2.54; 95% CI = 1.81-3.56). Certain sociodemographic variables, including the head of the family (PR = 1.52; 95% CI = 1.02-2.23), greater educational level of the head of the family (PR = 0.32; 95% CI = 0.17-0.61), and female sex (PR = 1.40; 95% CI = 1.05-1.89), had negative associations with QOL. We conclude that malocclusion has a negative impact on the QOL of adolescents, associated with socioeconomic conditions and the cosmetic effects of malocclusion.