Objectives: the aims of this study were the development of a novel questionnaire to assess the impact of prosthetic treatments on oral health-related quality of life (OHRQoL) and the performance of a prospective pilot study. Background: the currently preferred OHRQoL measurement tool is the oral health impact profile-49 (OHIP-49), a self-report questionnaire which mainly focuses on general effects related to oral health. Materials and methods: A total of 24 adult participants (9 females and 15 males) were recruited and asked to complete the novel questionnaire twice: once before the prosthetic treatment began and 4–6 weeks post-treatment. The assessment of the change in OHRQoL was based on the differences in participants’ answers before and after treatment. Data were analyzed using ANOVA with a repeated-measures method and t-tests. The reliability of the questionnaire was tested using Cronbach’s alpha and intraclass coefficient (ICC). Results: The questionnaire was found to be reliable (α ≥ 0.6), with “social disability” having the highest score (α = 0.868). All domains showed an improvement (α < 0.005) in OHRQoL scores after treatment. Conclusions: the novel questionnaire tested in this study was found to be reliable and convenient to use, and demonstrated that prosthetic treatments have a significant positive effect on OHRQoL post-treatment scores.