Ankylosing spondylitis (AS) is a human leukocyte antigen (HLA)-B27-associated chronic inflammatory disease of unknown etiology. There are few effective treatments for ankylosing spondylitis, which causes substantial morbidity. The relationship between AS and enterobacteria, especially Klebsiella pneumoniae, has been reported from several groups in several countries. We performed an open-label trial of moxifloxacin, a fluoroquinolone antibiotic, in patients with ankylosing spondylitis. Treatment with moxifloxacin resulted in significant and sustained improvement. At 12 weeks, patients treated with moxifloxacin had significantly greater improvement in primary outcome measures (P < 0.001). The moxifloxacin group also had significantly greater improvement in many of the secondary outcome measures (P < 0.001). In this twelve-week trial, moxifloxacin was safe, well tolerated, and associated with improvement in the inflammatory symptoms of AS.