To manage intra-fractional motions, recent developments in tomotherapy enable a unique capability of adjusting MLC/jaw to track the moving target based on the intra-fractional motions detected by sequential monoscopic imaging. In this study, we evaluated the effectiveness of motion compensation with a realistic imaging rate for prostate stereotactic body radiotherapy (SBRT). The obtained results will guide optimizing treatment parameters and image-guided radiation therapy (IGRT) in tomotherapy using this approach.Ten retrospective prostate cases with actual prostate motion curves previously recorded through the Calypso system were used in this study. Based on the recorded peak-to-peak motion, these cases represented either large ( 5 mm) or median (≤ 5 mm) intra-fractional prostate motions. All the cases were re-planned on tomotherapy using 35 Gy/5 fractions SBRT regimen and three different jaw settings of 1 cm static, 2.5 cm static, and 2.5 cm dynamic jaw. Two motion compensation methods were evaluated: a complete compensation that adjusted the jaw and MLC every 0.1 s (the same rate as the Calypso motion trace), and a realistic compensation that adjusted the jaw and MLC at an average imaging interval of 6 s from sequential monoscopic images. An in-house 4D dose calculation software was then applied to calculate the dosimetric outcomes from the original motion-free plan, the motion-contaminated plan, and the two abovementioned motion-compensated plans. During the process, various imaging rates were also simulated in one case with unusually large motions to quantify the impact of the KV-imaging rate on the effectiveness of motion compensation.The effectiveness of motion compensation was evaluated based on the PTV coverage and OAR sparing. Without any motion-compensation, the PTV coverage (PTV V100%) of patients with large prostate motions decreased remarkably to 55%-82% when planning with the 1 cm jaw but to a less level of 67-94% with the 2.5 cm jaw. In contrast, motion compensation improved the PTV coverage (92%) when combined with the 2.5 cm jaw, but less effective, around 75%-94%, with the 1 cm jaw. For OAR sparing, the bladder D1cc, bladder D10cc, and rectum D1cc all increased in the motion-contaminated plans. Motion compensation improved OAR sparing to the equivalent level of the original motion-free plans. For patients with median prostate motion, motion-induced degradation in PTV coverage was only observed when planning with the 1 cm jaw. After motion compensation, the PTV coverage improved to better than 94% for all three jaw settings. Additionally, the effectiveness of motion compensation depends on the imaging rate. Motion compensation with a typical rate of two KV images per gantry rotation effectively reduces motion-induced dosimetric uncertainties. However, a higher imaging rate is recommended when planning with a 1 cm jaw for patients with large motions.Our results demonstrated that the performance of sequential monoscopic imaging-guided motion compensation on tomotherapy depends on the amplitude of intra-fractional prostate motion, the plan parameter settings, especially jaw setting, gantry rotation, and the imaging rate for motion compensation. Creating a patient-specific imaging guidance protocol is essential to balance the effectiveness of motion compensation and achievable imaging rate for intra-fractional motion tracking.