In the context of clinical trials, measurement of change is critical. The aim of this study was to determine the minimally important difference (MID) for the Oral Health Impact Profile-20 (OHIP-20) when used with partially dentate patients undergoing treatment that included the provision of removable partial dentures. In a prospective clinical trial, 51 consecutive patients were provided with removable partial dentures. In addition to demographic and dental status data, patients completed an OHIP-20 prior to treatment. One month postoperatively, patients completed a post-treatment OHIP-20 and a global transition scale. Domains assessed in the global transition scale were appearance, ability to chew food, oral comfort, and speech. The MID for the OHIP-20 was calculated using the anchor-based approach. From the initial sample of 51 patients, 44 completed post-treatment questionnaires and were included in the analysis. Change scores in the four transition domains indicated that new dentures had a positive impact in the majority of subjects, especially in perceived impact on chewing and appearance. The study provided a guideline as to what constitutes the MID for the OHIP-20. This benchmark can be used when interpreting the impact of clinical intervention for replacing missing teeth and for power calculation in statistical analyses.