OBJECTIVE: In this randomized controlled trial, we compared the effect of celecoxib and acetaminophen on pain and magnetic resonance imaging (MRI) scores in patients with chronic nonspecific low back pain. METHODS: A total of 50 patients with chronic nonspecific low back pain were blindly randomized into 2 groups treated with celecoxib (200 mg twice daily) or acetaminophen (500 mg twice daily). Outcome measures included total back pain, nocturnal back pain, Oswestry Disability Index (ODI) scores, the Short Form 36 health survey to assess physical and mental status, and patient global assessment. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Metrology Index scores were also assessed before and after the therapy. The Spondyloarthritis Research Consortium of Canada scoring method was used to evaluate spinal MRI changes. RESULTS: Celecoxib showed a superior effect on total back pain, ODI, BASDAI, nocturnal back pain, and patient global assessment, compared to acetaminophen (P < 0.05). The number of patients with a significant change in back pain scales was higher in the celecoxib arm (ODI 34.8% versus 4.5%, nocturnal back pain 41.7% versus 9.1%, total back pain 33.3% versus 9.1%, and BASDAI 30.4% versus 9.1%; P < 0.01 for all). The responsiveness to celecoxib, calculated by Guyatt's Responsiveness Index, was 1.62, 1.28, 1.27, and 0.58 for the ODI, total back pain, BASDAI, and nocturnal back pain, respectively. The MRI scores for sacroiliac joints and spine showed no significant change with either treatment when compared with baseline values (P > 0.05). CONCLUSION: There was superior efficacy of celecoxib compared with acetaminophen in chronic nonspecific low back pain. Inflammatory lesions of sacroiliac joints and spine are commonly seen in nonspecific low back pain, but these lesions did not change with either celecoxib or acetaminophen treatments and were not associated with clinical response to either agent.