The purpose of the current study was to assess the oral health related quality of life (OHRQoL), general health related quality of life (HRQoL), clinical oral and denture status, as well as their interrelation, within a hospitalized general population. The Romanian versions of the Oral Health Impact Profile-49 (OHIP-49Ro), SF-36 questionnaires, together with an additional set of oral health assessment questions, were administered under the interview format to 170 patients, hospitalized in the Second Medical Clinic of Internal Medicine, Cluj-Napoca, Romania. The patients also underwent clinical examination, based on which the DMFT was calculated. Denture status, was as well, registered, together with the denture material. Each patient provided informed consent, prior to any examination. Questionnaire scores were calculated and used for the univariate descriptive statistics, reflecting oral health, OHRQoL and HRQoL sample tendencies. Successively, multiple regression analysis was applied, with the purpose of investigating the relationship between: the clinical oral health status, OHRQoL and HRQoL. In the first model, OHRQoL, while in the second model the dependent variable was represented by the HRQoL, each having a set of established predictors. Additionally, for denture wearing patients, OHRQoL variations in respect to the denture material were assessed, using one-way ANOVA. The mean OHIP-49Ro overall score was 31.90. The mean SF-36 subscales score was 60.66. The mean DMFT score was 18.47. For both regression analyses, all the regression models were significant. For the first model, the predictors accounted for 48.5% of variance in OHRQoL. For the second model, the highest percent of variance, explained by the predictors, was registered for the Mental Health subscale (22.8%). DMFT, as a clinical measure, was a statistically significant predictor rather for the perception in general health. However, OHRQoL was a good predictor for HRQoL, as an integrated part of it. Moreover, the one-way ANOVA indicated statistically significant differences in OHRQoL perception, in respect to the denture material F(2, 82) = 3.253, p = 0.044. The current study indicated complex relations between the patients� clinical status, the OHRQoL and HRQoL. The clinical determinants presented direct impact on both OHRQoL and HRQoL. More balanced HRQoL scores suggested that patients focused more on the perception of general health outcomes.