Chemoradiotherapy (CRT) is considered the standard treatment for anal canal cancer. However, the optimum schedule of therapy has yet to be defined. This study was carried out to evaluate the role of dose intensity (DI) of chemotherapy (ChT) and radiotherapy (RT) on the outcome of patients submitted to CRT. Thirty-five consecutive patients with anal canal carcinoma received a combination of RT (median dose 56 Gy) and ChT (two or more cycles of 5-fluorouracil and mitomycin C). With a median follow-up of 33 months, 83% of patients are alive without evidence of disease and 70% are colostomy-free. Five-year actuarial disease-free survival (DFS) is 74%. Univariate and multivariate analysis was performed to determine the correlation of DFS with various clinical and therapeutic parameters. Our series confirmed the prognostic negative value of a tumor size >4 cm. An average relative dose-intensity (ARDI) >0.8 was related to a better outcome both in univariate and in multivariate analysis; an overall treatment time >70 days was related to a worse DFS in univariate analysis, but these data were not confirmed by the Cox model. RT dose was not associated with DFS. In conclusion, the results of this study seem to suggest an independent prognostic role of ChT DI, as measured by ARDI. The results regarding RT DI are inconclusive, and remain a matter for further trials.