Patient-Reported Outcomes Measurement Information System (PROMIS) instruments can provide valid, interpretable measures of health status among adults with osteoarthritis (OA). However, their ability to detect meaningful change over time is unknown. We evaluated the responsiveness and minimally important differences (MID) for four PROMIS Short Forms: Physical Function, Pain Interference, Depression, and Anxiety. We analyzed adults with symptomatic knee OA from our randomized trial comparing Tai Chi and physical therapy. Using baseline and 12-week scores, responsiveness was evaluated according to consensus standards by testing 6 a priori hypotheses of the correlations between PROMIS and legacy change scores. Responsiveness was considered high if ≥5 hypotheses were confirmed, and moderate if 3 or 4 were confirmed. MIDs were evaluated according to prospective change for people achieving previously-established MID on legacy comparators. The lowest and highest MIDs meeting a priori quality criteria formed an MID range for each PROMIS Short Form. Among 165 predominantly female (70%) and white (57%) participants, mean age was 61 years and body mass index was 33kg/m2. PROMIS Physical Function had 5 confirmed hypotheses and Pain Interference, Depression, and Anxiety had 3 or 4. MID ranges were: Depression=3.0–3.1; Anxiety=2.3–3.4; Physical Function=1.9–2.2; and Pain Interference=2.35–2.4. PROMIS Physical Function has high responsiveness, and Depression, Anxiety, and Pain Interference have moderate responsiveness among adults with knee OA. We established the first MIDs for PROMIS in this population, and provided an important standard of reference to better apply or interpret PROMIS in future trials or clinical practice.