Purpose Preoperative short-course radiation therapy (SCRT) has rarely been used for rectal cancer in the United States, although 2 randomized phase 3 trials demonstrate equivalence to conventional chemoradiation (CRT), and recent updates to national guidelines include this regimen as a treatment option. We sought to evaluate the efficacy and safety of preoperative SCRT followed by immediate surgery within 1 week to treat rectal cancer in the US setting. Methods and materials All patients treated with preoperative SCRT (4 Gy × 5 fractions for total 20 Gy) followed by planned surgery within 1 week at our institution were retrospectively evaluated. Censored cases with ≥2 years of follow-up were included along with any disease failure or death. Patients with cM1 disease were excluded. Patients with yp stage II/III disease typically received adjuvant chemotherapy from the 1990s onwards. The primary outcomes were actuarial (Kaplan-Meier) 5-year locoregional control (LC), disease-free survival (DFS), and overall survival (OS) as well as late severe (greater than or equal to grade 3) toxicity. Results Our analysis included 202 consecutive patients with clinical stage I-III disease treated from 1977 through 2011. Median follow-up was 6.5 years (range, 2-29.2). Five-year disease outcomes were 95.9% ± 1.5% for LC, 76.4% ± 3.1% for DFS, and 84.6% ± 2.6% for OS. For patients with locally advanced rectal cancer (cT3-4 and/or cN+), 5-year LC, DFS, and OS were 95.1% ± 2.1%, 73.3% ± 4.3%, and 80.6% ± 3.7%, respectively. The late severe toxicity rate was 11.4%. Conclusions SCRT followed by immediate surgery is a safe and effective treatment for patients with rectal cancer in the United States. Though SCRT has not been widely adopted, recent updates to the national guidelines for rectal cancer as well as financial pressures to reduce healthcare costs may lead to increased utilization of this treatment regimen in the future.