BACKGROUND: Patient-reported outcomes (PROs) are the gold standard for reporting clinical outcomes in research. A crucial component of interpreting PROs is the minimum clinically important difference (MCID). Patient-Rated Wrist Evaluation (PRWE) is a disease-specific PRO tool developed for use in distal radius fractures. The purpose of this study was to determine the influence of injury characteristics, treatment modality, and calculation methodology on the PRWE MCID in distal radius fractures. We hypothesize the MCID would be significantly influenced by each of these factors. METHODS: From 2014 to 2016, 197 patients with a distal radius fracture were treated at a single level I trauma center. Each patient was asked to complete a PRWE survey at preoperative baseline, 6-week postoperative, and 12-week postoperative dates. The MCID was derived utilizing 2 distinct strategies, anchor and distribution. Anchor questions involved overall health anchor and mental and emotional health anchor. Patient variables regarding demographics, injury characteristics, and treatment modality were collected. RESULTS: The MCID was unique between analytical methods at all time points. The distribution MCID presented commonality across assessed variables. However, the anchor MCID was unique by AO/OTA fracture classifications, treatment modality, and time points. CONCLUSIONS: Our study found the MCID was heavily influenced by assessment time points, analytical method, treatment modality, and fracture classification. These results suggest that to accurately interpret PRO data in clinical trials, an anchor question should be included so that the MCID can be determined for the specific patient population included in the study.