OBJECTIVES: Interpretation of patient-reported outcomes (PROs) requires some definition of an important or meaningful difference. This study aimed to estimate minimally important differences (MIDs) for the Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue and Pain Interference scale scores in rheumatoid arthritis (RA).  METHODS: The responsiveness of several PROs was assessed in an observational cohort of 521 RA patients in the Arthritis, Rheumatism and Aging Medical Information Systems (ARAMIS) cohorts. PROMIS Fatigue and Pain Interference instruments were administered at baseline, 6 months, and 12 months. Self-reported retrospective changes in fatigue and pain over the previous 6 months were obtained at the follow-ups (a lot better/worse, a little better/worse, stayed the same). We estimated MIDs using the mean change in PROMIS scores for people who rated their change ‘a little better’ or ‘a little worse.’  RESULTS: At 6 months, 41 patients reported their fatigue was a little better compared to baseline (mean change [SD]: -2.6 [4.8]), 119 a little worse (1.7 [5.6]). Pain was a little better for 60 patients (-1.9 [6.1]) and a little worse for 126 (0.6 [5.7]). At 12 months, fatigue was a little better compared to 6 months prior for 31 patients (-1.3 [6.5]) and a little worse for 133 (0.9 [5.6]). Pain was a little better for 53 patients (-1.8 [5.7]) and a little worse for 122 (1.5 [5.0]).  Thus, the MID range was 1-2 points for both Fatigue and Pain Interference. Correlations between change scores and retrospective ratings were low (0.13-0.29), indicating that these analyses may underestimate the MID.  CONCLUSIONS: The MID for PROMIS Fatigue and PROMIS Pain Interference, estimated from this cohort of RA patients, is roughly 2 points and corresponds to a small effect size. This is consistent with earlier work in this cohort demonstrating an MID of 2 points for PROMIS Physical Functioning.