In the etiology of non-malignant pain, a significant proportion is constituted by patients with pain originating in the musculoskeletal system. Th e use of strong opioids in the treatment of non-malignant pain is still controversial. Therefore, the aim of this study was to establish the efficacy and safety of oxycodone with a controlled release of the active substance (CR) in the treatment of patients with chronic, not well-controlled musculoskeletal pain. Here we present our preliminary results. In this prospective, open, single-center study conducted at a rheumatology center we enrolled consecutive patients with musculoskeletal pain due to a variety of musculoskeletal diseases (osteoarthritis, pain in the lower back, spondyloarthritis), who suffered from moderate to severe pain despite previous analgesic therapy (with NSAIDs, weak opioids, or a fixed combination of paracetamol and weak opioids). Patients were switched to therapy with oxycodone CR and followed for 14 days. The starting dose of oxycodone CR was 10 mg, and later the dose was adapted as necessary. The primary endpoint was to assess the effectiveness of oxycodone CR on pain intensity, and the secondary goal was to assess the efficiency on the general health of the patient (both on a horizontal visual analogue scale, VAS 0 = best, 10 = worst). Fifteen patients (12 women, 3 men), with a mean age of 61 ± 12 years and a diagnosis of osteoarthritis, pain in the lower back, or inflammatory arthritis, were included in the study. Th e duration of pain was 41 ± 12 months. The average intensity of pain before oxycodone CR treatment was 7.87 ± 2.28 (range 7-10), and at the end of the study it was 5.92 ± 2.43 (range 4-9) (p=0.069). General health was rated 7.27 ± 2.14 (range 3-10) before the start and 6.00 ± 1.53 (range 3-9) at the end of the study (p=0.028). In one patient the treatment was discontinued due to dizziness and nausea, and one patient voluntarily left the study because of fear and the subjective impression of no adequate pain control after 2 days of treatment. The oxycodone side-effect profile was as expected. Results of our preliminary study show that in patients with chronic non-malignant pain which is not well controlled by simple analgesics, NSAIDs, and weak opioids, treatment with oxycodone CR contributed to a significant reduction in the level of pain and improved the general health of the subjects.