Successful treatment of severe Clostridium difficile colitis has been reported with the use of adjunctive intracolonic vancomycin (ICV) therapy. We report a descriptive case series and review the literature on patients with C. difficile colitis who received adjunctive ICV therapy. Nine patients received antibiotics within 6 weeks prior to presentation. Complete resolution of the clinical presentation occurred in 8 patients (88.9%), and eradication of C. difficile cytotoxin production was documented in 3 (75%) of 4 patients who were tested after the completion of adjunctive ICV therapy. One patient (11.1%) died as a result of progressive multisystem organ failure. In the 6 weeks after the completion of treatment for C. difficile colitis, no patient had recurrent disease, required surgical intervention, or experienced complications from adjunctive ICV therapy. In this case series, administration of adjunctive ICV therapy appeared to be a safe, practical, and effective adjunctive therapy for severe C. difficile colitis.