Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-kilovolt (kV) x-ray intraoperative radiotherapy (IORT) can achieve promising results compared with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from low-kV x-ray IORT. We retrospectively reviewed 44 patients with pT3 LACC treated with low-kV x-ray IORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from low-kV x-ray IORT. The Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression-free survival (PFS). Correlation analysis was used to discover the association of multiple factors to the results of treatment represented by the values of OS and PFS. The median follow-up of patients was 20.5 months (range, 6.1-38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort was 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the low-kV x-ray IORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0%, and the morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30 days) and three late complications (> 30 days) leading early and late morbidity rates of 9% and 7%, respectively. Patients with LACC who had undergone an additional low-kV x-ray IORT can achieve encouraging locoregional control, PFS, OS, and distant control without an increase in short-term or long-term complications. Low-kV x-ray IORT can be considered as part of management in pT3 LACC.