Background: To assess whether structure-based medical acupuncture (SMA) can improve Patient-Reported Outcomes Measurement Information System (PROMIS) scores in patients presenting with musculoskeletal pain. Methods: An audit was conducted of all patients presenting with musculoskeletal pain treated by a single provider with SMA in 2017. Inclusion criteria included a pre-treatment and at least one post-treatment PROMIS score. Patient demographics and previous treatments tried were recorded. Documented events other than acupuncture that were thought to interfere with PROMIS scores were recorded, and no further scores were used after these events. A maximum of nine visits after the initial visit were used. The PROMIS domains assessed included anxiety, depression, pain interference and physical function. Results: Seventy-two patients who had been treated with SMA met the inclusion criteria. Sixty-five of the patients (90%) had chronic pain. For their presenting complaint, 59 (82%) had previously sought treatment from another non-operative provider, 60 (83%) had tried physical therapy, and 20 (28%) had even had surgery. Despite this, SMA appeared to be able to significantly improve PROMIS anxiety at visits 1–3 and PROMIS depression at visit 3. After just one treatment, minimal clinically important differences (MCID) were reached in 32%–44% of patients for PROMIS anxiety, 17%–36% for PROMIS depression, 28%–29% for PROMIS physical function, and 21%–36% for PROMIS pain interference, based on low and high cut-offs of a range of quoted MCID values. Conclusion: In a difficult patient population with musculoskeletal pain, SMA is a technique that can likely be used to improve PROMIS anxiety and depression, although no firm conclusions can be drawn from this uncontrolled clinical audit. Of note, MCIDs were sometimes obtained even after just one treatment.