Background and Objectives: Stages II and III rectal tumors are known as locally advanced rectal cancer (LARC) because they are characterized by a high incidence of local and distant relapses and a low probability of long-term survival. Adjuvant treatments have been advocated to ameliorate overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) without a univocal beneficial trend. The aim of this study was to identify the independent predictive factors of OS, LRFS, and MFS which could best select patients for adjuvant treatment of LARC. Methods: Of 153 rectal cancer cases seen consecutively from 1991 to 1998, we studied the main clinical and pathological parameters of 73 LARCs. Clinical and pathological variables were studied by univariate analysis, and independent predictive factors were identified by multivariate analysis. Results: Stages II and III rectal cancer have shown not statistically different rates of OS, LRFS, and MFS. Factors independently associated with increasing OS and MFS were low preoperative carcinoembryonic antigen level (CEA), low number of metastatic lymph nodes, low percentage of metastatic lymph nodes out of the total number of lymph nodes excised, and adjuvant treatment. Increased staging and distal resection margins ≤ 1 cm were shown to be independent detrimental risk factors regarding OS and MFS, respectively. Independent prognostic factors associated with a reduction in LRFS were advanced age, Hartman's resection, distal resection margins ≤ 1 cm, and fewer than 14 resected nodes. Conclusions: Whereas stage I rectal cancer can be treated with a good probability of cure by surgery alone, avoiding adverse effects of adjuvant regimens, the outcome of LARC appears to be positively influenced by adjuvant therapies. In LARC, an accurate study of risk factors would be useful to identify which subset of patients could be favorably influenced by postoperative radiochemotherapy.