Purpose:The purpose of he study was to reduce setup errors during intensity-modulated radiation therapy (IMRT) with an original knee fixation device (KFD) and evaluate the clinical target volume (CTV) coverage.Methods:Participants were classified into two groups: knee flexion (KF) group (n = 16), wherein participants' knees were fixed in a flexed position using the proposed KFD during planning computed tomography, and knee extension group (KE; n = 15), wherein no KFD was used. We investigated the residual rotational errors and inter-fractional setup errors with or without KFD. Furthermore, inter-fractional margins were calculated using logistic regression analysis, and CTV coverage was evaluated.Results:The residual rotational errors in the yaw and roll directions (P < 0.02) and the inter-fractional error in the anterior-posterior (A-P) direction (P < 0.02) improved significantly in the KF group compared with the KE group. Repeatability was improved for the pitch direction. The inter-fractional margins were 6.68 mm and 4.87 mm in the A-P and superior-inferior (S-I) directions, respectively, in the KF group, representing reductions (mm) of 20.8% and 12.6% compared with the KE group, respectively. The odds ratios for CTV coverage in the KF group compared to the KE group were 2.76 (P < 0.001) and 1.74 (P < 0.05) in the A-P and S-I directions, respectively.Conclusions:The IMRT fixation method using an original KFD improved the residual rotational error in the three directions and the inter-fractional error in the A-P direction, reduced the interfractional margins in the A-P, and S-I directions and improved CTV coverage. Our original KFD may be a useful fixation method during prostate IMRT.