Purpose: To develop a Dutch–Flemish translation of the PROMIS® upper extremity (PROMIS-UE) item bank v2.0, and to investigate its cross-cultural and construct validity as well as its floor and ceiling effects in patients with musculoskeletal UE disorders. Methods: State of the art translation methodology was used to develop the Dutch–Flemish PROMIS-UE item bank v2.0. The item bank and four legacy instruments were administered to 205 Dutch patients with musculoskeletal UE disorders visiting an orthopedic outpatient clinic. The validity of cross-cultural comparisons between English and Dutch patients was evaluated by studying differential item functioning (DIF) for language (Dutch vs. English) with ordinal logistic regression models and McFadden’s pseudo R2-change of ≥ 2% as critical value. Construct validity was assessed by formulating a priori hypotheses and calculating correlations with legacy instruments. Floor/ceiling effects were evaluated by determining the proportion of patients who achieved the lowest/highest possible raw score. Results: Eight items showed DIF for language, but their impact on the test score was negligible. The item bank correlated, as hypothesized, moderately with the Dutch–Flemish PROMIS pain intensity item (Pearson’s r = − 0.43) and strongly with the Disabilities of the Arm, Shoulder and Hand questionnaire, Subscale Disability/Symptoms (Spearman’s ρ = − 0.87), the Functional Index for Hand Osteoarthritis (ρ = − 0.86), and the Michigan Hand Outcomes Questionnaire, Subscale Activities of Daily Living (ρ = 0.87). No patients achieved the lowest or highest possible raw score. Conclusions: A Dutch–Flemish PROMIS-UE item bank v2.0 has been developed that showed sufficient cross-cultural and construct validity as well as absence of floor and ceiling effects.