We undertook a retrospective analysis of colonic spirochetosis in 14 cases: females, 3; males, 11; children, 4; adults, 10. Two men had HIV infections. All children and both HIV-infected men had abdominal complaints, diarrhea, or both. Most other adults underwent colonoscopy for polyp screening (n = 4) or follow-up of Crohn disease (n = 1) or had other indications (n = 2) or diarrhea (n = 1). Histologically, spirochetosis was identified in all parts of the colon and was not strongly associated with active inflammation, mucosal injury, or changes of chronicity. Genotype analysis of 13 cases showed that 11 resulted from Brachyspira aalborgi and 2 from Brachyspira pilosicoli infections. Only 2 patients were treated specifically with antibiotics, with complete resolution of abdominal symptoms in 1 patient with follow-up. Follow-up biopsy result were available for 2 patients who did not receive treatment; one showed persistent spirochetosis, and the other was negative. Spirochetosis in this series had a male predominance, was generally caused by B aalborgi, and occurred in 2 distinct clinical settings: children who often have abdominal symptoms and adults who typically are asymptomatic. While treatment information remains limited, treatment can lead to resolution of symptoms in some cases.