PURPOSE: Hypoxia is an important marker for resistance to therapy. In this study, we quantify the macroscopic effects of R2* mapping in prostate cancer patients incorporating susceptibility matching and field strengths effects. MATERIALS AND METHODS: 91 patients were scanned without endorectal coil (ERC) at 3T. Only when rectal gas was absent, data was included for analysis. Another group of 10 patients was scanned using a susceptibility matched ERC. To assess the residual contamination of R2 and macroscopic field non-uniformities, a group of 10 patients underwent ultra-high resolution 7T MRI. RESULTS: Of the patients scanned at 3T 60% presented rectal gas and were excluded, due to susceptibility artifacts. At 3T the tumor was significantly different (P<0.01) from the healthy surrounding tissue in R2* values at intrapatient level. Using the measured median R2* value of 24.9s(-1) at 3T and 43.2s(-1) at 7T of the peripheral zone, the minimum contribution of macroscopic susceptibility effects is 15% at 3T. CONCLUSION: R2* imaging might be a promising tool for hypoxia imaging, particularly when minimizing macroscopic susceptibility effects contaminating intrinsic R2* of tissue, such as rectal gas. At 3T macroscopic effects still contribute 15% in the R2* value, compared to ultra-high resolution R2* mapping at 7T