Introduction <p>Psychometric properties of the Patient-Reported Outcomes Measurement Information System^® Profile 29 (PROMIS-29) Norwegian version has previously been examined in a general population. This multicenter study aimed to examine the internal consistency, construct validity, responsiveness, score distribution and floor/ceiling effects of PROMIS-29 v2.1 in a Norwegian rehabilitation context.</p> Methods <p>Patients receiving rehabilitation services participating in a longitudinal cohort study answered PROMIS-29 at baseline and at 3-month follow-up. Internal consistency was assessed by Cronbach’s alpha and McDonald’s omega. Construct validity was examined through hypothesis testing, using EQ-5D-5L as comparator measure. Hypotheses for correlations of change scores for both questionnaires were tested as an expression of responsiveness. Score distribution and floor/ceiling effects were examined with histograms and descriptive statistics.</p> Results <p>A total of 828 patients with a mean age of 54.3 years were included for analysis. The internal consistency for each PROMIS-29 domain was confirmed, with alpha and omega values exceeding the threshold of ≥ 0.70. Regarding correlations between PROMIS-29 and EQ-5D-5L, 34 out of 40 hypotheses were confirmed for construct validity and 19 out of 24 for responsiveness, both meeting our a priori criterion of ≥ 75% confirmed hypotheses. There was no floor effect of any PROMIS-29 domain in our sample, and ceiling effect only for anxiety and depression domain scores. Still, this confirmed the applicability of PROMIS-29 in a rehabilitation context.</p> Conclusion <p>The Norwegian PROMIS-29 has sufficient internal consistency, construct validity and responsiveness for use as an outcome measure for health status and health-related quality of life in rehabilitation.</p> Trial registration number <p>ClinicalTrials.gov NCT03764982 RehabNytte study, registered 2018-12-04.</p>