Although researchers and clinicians are encouraged to use health-status questionnaires to evaluate, monitor, and modify care, their use is hindered by the lack of reference values. Without reference values, it is difficult to interpret or evaluate questionnaire scores. In this paper, we present reference values for the Musculoskeletal Function Assessment, a 101-item health-status questionnaire designed and validated for patients with a broad range of musculoskeletal disorders. We describe reference values for two samples: non-patients (n = 123) and patients with isolated extremity injuries (n = 274). For the non-patient sample, descriptive statistics are presented by age and gender, measured at one point in time. For the patient sample, descriptive statistics are provided for seven Orthopaedic Trauma Association/AO diagnostic groups, measured at two points in time. Reference values for changes in the Musculoskeletal Function Assessment total score are described for patients 3 and 9 months and 6 and 12 months after injury, The total scores by post-injury interval, across the diagnostic groups, are significantly better at follow-up than at baseline (p = 0.00). Reference values for changes in total scores are also described in terms of these diagnostic groups across post-injury intervals. Musculoskeletal Function Assessment total scores for Orthopaedic Trauma Association/AO diagnostic groups are significantly better at follow-up than at baseline (p < 0.03). Changes in the total score are also tested for responsiveness with use of standardized response means. Large effects are demonstrated for patients completing the Musculoskeletal Function Assessment at 3 and 9 months (1.03), and small effects are demonstrated for those completing it at 6 and 12 months (0.49). Moderate and large effects are demonstrated for Orthopaedic Trauma Association/AO diagnostic groups across post-injury intervals.