The intestinal microbiota might contribute to enteropathy associated with use of non-steroidal anti-inflammatory drugs (NSAIDs), but there have been few human studies of this association. We performed a placebo-controlled study to determine whether a delayed release antibiotic formulation (rifaximin-EIR) prevented development of intestinal lesions in persons taking daily NSAIDs. Sixty healthy volunteers (median age 26 years, 42% female) were given the NSAID diclofenac (75 mg twice daily) plus omeprazole (20 mg once daily), and either rifaximin-EIR (400 mg) or placebo, twice daily for 14 days.