Interest in image-guided radiation therapy (IGRT) reflects the desire to minimize interfraction positioning variability. Using a kilovoltage (kV) imaging unit mounted to a traditional LINAC allows daily matching of kV images to planning digitally reconstructed radiographs (DRRs). We quantify and evaluate the significance of calculated deviation from the intended isocenter. Since September 2004, 117 patients with various malignancies were treated using the On-Board Imaging (OBI) system, with 2088 treatment sessions. Patients were positioned by the treating therapist; orthogonal images were then obtained with the OBI unit. Couch shifts were made, aligning bony anatomy to the initial simulation image. Routine port films were performed weekly (after that day's OBI session). Ninety percent of all lateral, longitudinal, and vertical shifts were less than 0.8 cm, 0.6 cm, and 0.7 cm, respectively. The median vector shift for each anatomic site was: 0.42 cm for head and neck, 0.40 cm for CNS, 0.59 cm for GU/prostate, and 0.73 cm for breast; shift magnitude did not change with successive OBI sessions. The use of OBI effectively corrects setup variability. These shifts are typically small and random. The use of OBI likely can replace weekly port films for isocenter verification; however, OBI does not provide field shape verification.