Background and Purpose: Oxalobacter formigenes (OF) may play a protective role in preventing calcium oxalate stones. This is the first prospective study to evaluate the effect of antibiotics on OF colonization. Intestinal colonization by OF is associated with reduced urinary oxalate excretion. Exposure to antibiotics may be an important factor determining rates of colonization. Materials and Methods: The effect of antibiotics on OF colonization was compared in two groups: A group receiving antibiotics for gastric infection with Helicobacter pylori (HP) and a group without HP whose members were not receiving antibiotics. OF colonization in stool was detected by oxalate degradation at baseline and after 1 and 6 months. Results: The prevalence at baseline of intestinal colonization with OF was 43.1% among all patients screened. Among the 12 patients who were positive for OF who did not receive antibiotics, 11 (92%) had OF on stool tests at 1 month and 6 months. Of the 19 participants who were positive for OF and who received antibiotics for HP, only 7 (36.8%) continued to be colonized by OF on follow-up stool testing at 1 and 6 months (P = 0.003 by Fisher exact test). Amoxicillin and clarithromycin caused 62.5% of subjects to become negative for OF at 1 month; 56.2% remained negative for OF at 6 months. Conclusions: Antibiotics for HP infection effectively reduced colonization with OF, an effect present at 1 and 6 months after treatment. The lasting elimination of OF could be associated with hyperoxaluria and be a factor in recurrent kidney stone disease.