PURPOSE: The aim of the study was to evaluate the efficacy and the toxicity of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally-advanced, resectable rectal cancer. METHODS: Thirty-five patients with locally-advanced rectal cancer (cT3/4, N-/+) were treated with capecitabine (825 mg/m2, twice daily for 7 days/wk) and concomitant RT (50.4 Gy/28 fractions). Surgery was performed 6-8 wk after completion of the chemoradiation followed by 4-6 cycles of adjuvant capecitabine monotherapy (1,250 mg/m2, twice daily for 14 days every 3 wk). RESULTS: The chemoradiation program was completed in all but 2 patients, for whom both capecitabine and RT were interrupted for 2 wk because of grade-3 diarrhea. A R0 resection under the principle of total mesorectal excision (low anterior resection, 26; intersphincteric resection, 6; abdominoperineal resection, 2) was performed in all but one patient with a low anterior resection with positive circumferential margin (R1). Primary tumor and node downstaging occurred in 57% and 60% of patients, respectively. The overall rate of downstaging, including both the primary tumor and node, was 77% (27 patients). A pathological complete response of the primary tumor was achieved in 4 patients (11%). No patient had grade-4 toxicity, and the only grade-3 toxicity developed was diarrhea in 2 patients (6%) during chemoradiation. During a median follow-up of 38 mo, distant metastases developed in 4 patients (multiple lung metastases, 2; aortocaval nodal metastases, 2), and another 2 patients showed local recurrence. The three-year disease-free survival was 83%. CONCLUSION: This study suggests that preoperative capecitabine-based chemoradiation therapy is an effective and safe treatment modality for the tratment of locally-advanced, resectable rectal cancer.