The knowledge on the determinants of oral health-related quality of life (OHQoL) is still fragmentary. The aim of this study was to examine the influence of different socio-economic, behavioral, and clinical variables on OHQoL in a cross-cultural patient sample in Germany and Canada. The study had a cross-sectional design. It was conducted at five examination sites at clinics managed by the Technische Universität Dresden (Germany) and the University of Alberta (Canada), with the sites representing different cultural and socio-economic variables. Incoming patients satisfying the defined inclusion and exclusion criteria were asked to participate. Subjects who had been to a dentist within the last 3 months were excluded to avoid bias related to recent experiences associated with ongoing treatment. OHQoL was measured with the 49-item version of the OHIP (Oral Health Impact Profile) questionnaire (OHIP-49) together with age, gender, attendance and a set of oral health variables. The OHIP questions are organized into seven dimensions: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. All questions refer to the experiences of the subject in the preceding 12 months. Descriptive, univariate, and multivariate methods were applied in data analysis. Based on the results of the multivariate logistic regression analysis, only gender, removable denture wearing, and treatment need in endodontics, surgery, and prosthetics remained as significant explanatory variables in the final model for impaired OHQoL. With the OHIP subscale handicap being the dependent variable, missing anterior teeth (regardless of replacement), treatment need in surgery, and the time of the last dental visit were significant indicators of high - i.e. unfavorable - scores. In this patient sample, impaired OHQoL was associated with several factors. The examination site, however, was not among the explanatory variables in the final models, as had been expected, thus indicating the absence of cross-cultural differences.