The aim of the present study was to investigate the effect of dental caries experience and the components of the decayed, missing and filled teeth (DMFT) index on oral health-related quality of life (OHRQoL) among adolescents in southern Brazil. A cross-sectional study was conducted with 509 adolescents aged 11–14 years enrolled at public schools in the municipality of Osório (southern Brazil). A calibrated examiner performed the clinical examination for caries (World Health Organization: DMFT index), malocclusion (Dental Aesthetic Index) and traumatic dental injuries [Andreasen et al., 2007]. The participants answered the Brazilian version of the Child Perceptions Questionnaire (CPQ11–14) - Impact Short Form, and their parents/guardians answered a structured questionnaire addressing demographic and socioeconomic characteristics. Data analysis involved Poisson regression with robust variance, with the calculation of rate ratios adjusted for potential confounding variables. High severity of dental caries experience exerted a significant impact on OHRQoL, even after controlling for socioeconomic and clinical factors (rate ratio 1.30; 95% confidence interval, CI 1.12–1.51). All OHRQoL domains were affected by untreated dental caries. The multivariate analysis demonstrated that the CPQ11–14 scores were 33% higher among adolescents with untreated caries (rate ratio 1.33; 95% CI 1.17–1.50) and 24% higher among those with missing teeth (rate ratio 1.24; 95% CI 1.06–1.47). No difference in OHRQoL was found between adolescents with filled teeth and those without dental caries. In conclusion, dental caries experience, untreated dental caries and missing teeth exerted a negative impact on OHRQoL among the adolescents.