Background: Measurement instruments should be validated for use in the population for which they are intended. The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) has been developed to measure impairment of health-related quality of life in patients with hand eczema. Objectives: To assess validity, reproducibility, responsiveness and interpretability of the Dutch version of the QOLHEQ. Methods: This was a prospective validation study in adult patients with hand eczema. At three time points (T 0 , baseline; T 1 , after 1–3 days; T 2 , after 4–12 weeks), data from the QOLHEQ and multiple reference instruments were collected. Scale structure was assessed using item response theory analysis and structural equation modelling (SEM). Single-score validity and responsiveness were tested with hypotheses on correlations with reference instruments. Concerning reproducibility, intraclass correlation coefficients (ICC agreement ) and standard error of agreement (SEM agreement ) were checked. Regarding interpretability, bands for severity of quality-of-life impairment were proposed. Also, smallest detectable change (SDC) and minimally important change (MIC) were determined. Results: At T 0 , 300 individuals participated in the study (54% were male, mean age 45 years). Rescoring of the scale structure fitted the Rasch model and the SEM. The ICC agreement was 0·91 (95% confidence interval 0·85–0·94) and the SEM agreement was 5·2 points. Of the a priori formulated hypotheses, 80% (single-score validity) and 64% (change scores for responsiveness) were confirmed. The SDC was 14·4 points and the MIC was 11·5 points. Conclusions: The Dutch version of the QOLHEQ has a good structural validity and reproducibility and has a high single-score validity and moderate responsiveness. An improvement of ≥ 15 points should be regarded as a real, important change within the Dutch population. What's already known about this topic?. The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) measures impairment of health-related quality of ...