OBJECTIVE: To investigate the effect of sequential eradication therapy on serum osteoprotegerin levels in patients with infection and co-existing inflammatory bowel disease (IBD). METHODS: Three groups of patients were involved in this observational cross-sectional study: IBD (n = 83), infection (HP, n = 68), and infection with co-existing IBD (HP + IBD, n = 52). These groups were compared with a normal control group (NC, n = 50). Serum osteoprotegerin, serum bone alkaline phosphatase (BALP), and fecal calprotectin (FC) levels were measured. RESULTS: Serum osteoprotegerin levels were significantly correlated with the simple endoscopic score for Crohn's disease and Mayo score for ulcerative colitis. The receiver operating characteristic analysis of osteoprotegerin revealed high values for the area under the curve, sensitivity, and specificity. Discriminant analysis illustrated that osteoprotegerin levels significantly differentiated patients with IBD from healthy controls. Osteoprotegerin and FC levels distinguished the IBD and HP + IBD groups from the NC and HP groups. CONCLUSIONS: Sequential eradication therapy did not affect serum osteoprotegerin levels in patients with infection and co-existing IBD. Serum osteoprotegerin elevation might be a marker for IBD development in patients with past or current infection.