Quantitative analysis of multi-parametric magnetic resonance (MR) images of the prostate, including T2-weighted (T2w) and diffusion-weighted (DW) images, requires accurate image registration. We compared two registration methods between T2w and DW images. We collected pre-operative MR images of 124 prostate cancer patients (68 patients scanned with a GE scanner and 56 with Philips scanners). A landmark-based rigid registration was done based on six prostate landmarks in both T2w and DW images identified by a radiologist. Independently, a researcher manually registered the same images. A radiologist visually evaluated the registration results by using a 5-point ordinal scale of 1 (worst) to 5 (best). The Wilcoxon signed-rank test was used to determine whether the radiologist's ratings of the results of the two registration methods were significantly different. Results demonstrated that both methods were accurate: the average ratings were 4.2, 3.3, and 3.8 for GE, Philips, and all images, respectively, for the landmark-based method; and 4.6, 3.7, and 4.2, respectively, for the manual method. The manual registration results were more accurate than the landmark-based registration results (p < 0.0001 for GE, Philips, and all images). Therefore, the manual method produces more accurate registration between T2w and DW images than the landmark-based method.