Purpose: The construct validity, test–retest reliability, and measurement error of the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) were examined. Additionally, the influence of administration-method on reliability and measurement error was investigated. Method: 112 Dutch adult MS-patients from an academic- and a residential care-facility participated. Questionnaires were administered on paper, online or as interview, and patients performed several performance tests. Construct validity was assessed by testing pre-defined hypotheses. Reliability was assessed using Intraclass Correlation Coefficients (ICCs), Standard Error of Measurements (SEMs) and Smallest Detectable Changes (SDCs). Results: For construct validity (N = 105) 9 of 13 hypotheses were confirmed (69%). As expected, the AMSQ showed moderate to strong relationships with the instruments measuring similar constructs. The test–retest reliability coefficient was 0.96 (95% Confidence Interval 0.94–0.97); SEM was 6.3 (6.3% of scale range); SDC was 17.5 (on a sale from 0 to 100). Different administration-methods showed good reliability (ICC 0.88–0.94) and small standard errors (SEM 5.6–7.2). Conclusion: The AMSQ shows satisfying results for validity and excellent reliability; allowing for proper use in research. Due to a large SDC value, caution is needed when using the AMSQ in individual patient care. Further research should determine whether the SDC is smaller than the minimal important change.Implications for Rehabilitation The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) measures activity limitations due to hand and arm functioning in patients with Multiple Sclerosis (MS). Results of this study confirm adequate validity and reliability of the AMSQ in patient with MS. The equivalence of scores from online, paper or interview administration is supported. A change score of ≥18 points on the scale of the AMSQ (on a scale 0–100) needs to occur to be certain a change beyond measurement error has occurred in an individual patient.