STUDY DESIGN: A cross-sectional study. OBJECTIVE: The aim of this study was to validate the Dutch-Flemish PROMIS Pain Interference item bank in patients with musculoskeletal complaints. SUMMARY OF BACKGROUND DATA: PROMIS item banks have been developed and validated in the US. They need to be further validated in various patient populations and in different languages. METHODS: One thousand six hundred seventy-seven patients answered the full item bank. A Graded Response Model (GRM) was used to study dimensionality with confirmatory factor analyses and by assessing local independency. Monotonicity was evaluated with Mokken scaling. An Item Response Theory (IRT) model was used to study item fit and to estimate slope and threshold parameters. Differential item functioning (DIF) for language, age, and gender was assessed using ordinal logistic regression analyses. DIF for language was evaluated by comparing our data with a similar US sample. Hypotheses concerning construct validity were tested by correlating item bank-scores with scores on several legacy instruments. RESULTS: The GRM showed suboptimal evidence of unidimensionality in confirmatory factor analysis [Comparative Fit Index (CFI): 0.903, Tucker-Lewis Index (TLI): 0.897, Root Mean Square Error of Approximation (RMSEA): 0.144], and 99 item pairs with local dependence. A bifactor model showed good fit (CFI: 0.964, TLI: 0.961, RMSEA: 0.089), with a high Omega-H (0.97), a high explained common variance (ECV: 0.81), and no local dependence. Sufficient monotonicity was shown for all items (Mokken H(i): 0.367-0.686). The unidimensional IRT model showed good fit (only two items with S-X < 0.001), with slope parameters ranging from 1.00 to 4.27, and threshold parameters ranging from -1.77 to 3.66. None of the items showed DIF for age or gender. One item showed DIF for language. Correlations with legacy instruments were high (Pearson R: 0.53-0.75), supporting construct validity. CONCLUSION: The high omega-H and the high ECV indicate that the item bank could be considered essentially unidimensional. The item bank showed good item fit, good coverage of the pain interference trait, and good construct validity.N/A.