Background: There are no randomized phase III trials comparing 5FU versus capecitabine in combination with mitomycin and RT for locally advanced anal cancer. Capecitabine has been increasingly adopted in substitution for infusional 5FU, based on data from other disease sites as well as the easier administration. In this retrospective cohort analysis, we aim to evaluate the outcomes of patients treated with both regimens. Methods: Patients with new histologic diagnosis of SCC of the anal canal who initiated curative-intent RT (50-54 Gy) with CM or FM between 1998 and 2013 at one of 6 provincial cancer centers in British Columbia were included. Their characteristics and outcomes were retrospectively analyzed. Differences in proportions were analyzed using the Chi-square test. Disease free survival was estimated using the Kaplan Meier method with log rank test for comparison. Results: A total of 300 patients (195 females) were reviewed. Median age was 58.5 (range 18-85). 34% of the patients were T3 or above and 29% were N2 or above. Median tumor size was 4 cm. Only 4.3% were HIV positive. 194 pts (64.6%) were treated with FM and 106 (35.3%) with CM. The groups were balanced for age, gender, histology, HIV status, T and N status. Median follow-up was 61.7 months (75.2 for FM and 15.8 for CM). Median DFS was not reached in both groups (p 0.24, HR 0.774). The remainder of response and outcomes are included in the Table. Conclusions: There is no difference between the two cohorts in this retrospective study. Additionally, there is a trend towards lower recurrence rates favoring capecitabine that may be explored in larger phase III studies. Capecitabine can be considered an alternative to 5FU in the chemoradiation treatment of SCC of the anus.