Introduction. Clostridioides difficile associated diarrhea (CDAD) is a major public health issue. The appendix may function as a reservoir for the intestinal microbiome, which may repopulate the intestine following enteric infections including CDAD. Patients/Methods. This retrospective cohort study includes a total of 12,039 patients undergoing appendectomy, hemicolectomy, and cholecystectomy at a single center between 1992 and 2011 who were diagnosed with early and late-onset CDAD and were followed for a minimum of two years. Results. Cumulative CDAD rates were 2.3% after appendectomy, 6.4% after left and 6.8% after right hemicolectomy, and 4% after cholecystectomy with a median onset of 76 (range 1–6011) days after the procedure. Median time to CDAD onset was 76 days after appendectomy, 23 days after left, 54 days after right hemicolectomy, and 122 days after cholecystectomy (
p
<
0.05
). Late-onset CDAD (>1 year) was significantly more common following appendectomy (37%) and cholecystectomy (39%) than after left (17%) and right (21%) hemicolectomy. Significant differences in age, gender, complication rate, and length of hospitalization between the four groups need to be considered when interpreting the results. Conclusion. The incidence of CDAD after various abdominal surgeries ranged between 2% and 7% in this study. Whereas, hemicolectomy patients had predominantly early onset CDAD, and appendectomy and cholecystectomy may increase the risk for late-onset CDAD. Appendectomy per se does not seem to increase the risk for late-onset CDAD.