Purpose: Locally advanced rectal adenocarcinoma is effectively treated with chemoradiation and surgery; however, 10 to 25% of patients locally recur within or near a previously irradiated field. Proton radiation therapy (PRT) is ideally suited to the problem of reirradiation for locally recurrent rectal cancer (LRRC). Patients and Methods: Seven patients with LRRC in or near prior radiation fields were enrolled on this prospective study from March 2010 to February 2011. All patients underwent positron emission tomography (PET)/computed tomography (CT) simulation and were stratified by low volume (clinical target volume,250 cm 3 , n¼4) or high volume (.250 cm 3 , n¼3). Primary endpoints were feasibility and acute toxicity (within 90 days from PRT initiation). Dosimetry was compared using the Wilcoxon signed-rank test. Tumor response was defined according to PERCIST criteria. Results: Median follow-up was 14 months (4.9-22.6). Median dose of prior RT was 5040 cGy. Mean PRT dose was 6120 cGy (RBE) (range, 4500-6480 cGy). The total dose sum of prior radiation therapy treatment and PRT was 109.8 Gy (RBE) (range, 95.4-151.2). One patient had surgery prior to and 1 after PRT. Six patients received concurrent 5-fluorouracil-based chemotherapy. Bowel volume receiving 10 and 20 Gy, and the dose to 200 and 150 cm 3 of bowel were significantly reduced. There were 3 acute grade 3 and 3 late grade 4 toxicities. Four patients were alive at time of follow-up. Six had a metabolic complete response, of whom 2 subsequently locally recurred. One had initial progressive disease. Of 6 symptomatic patients, 3 had complete pain resolution and 3 partial.Conclusions: This preliminary report indicates that PRT for LRRC provides dosimetric improvements over intensity-modulated radiation therapy, particularly to the bowel. The modest rates of acute and late toxicity as well as the preliminary outcomes of high tumor and symptom control rates are promising.