The aim of this study was to reproduce relaxivity-iron calibration in hepatic iron overload using a Monte Carlo model, and further extend the model with multiple spin echo (MSE) imaging. As previously reported, relationships between relaxation rates (R Ã 2 and single spin echo R 2 ) and liver iron concentration (LIC) can be characterized by a Monte Carlo model incorporating realistic liver structure, iron distribution, and proton mobility. In this study, relaxivity-iron calibration curves at 1.5 and 3.0 T were simulated using the Monte Carlo model. Furthermore, the model was extended with MSE imaging, and iron calibrations were evaluated using two different fitting models: mononexponential with a constant offset and nonmonoexponential. Results consistent with previous empirical calibrations and Monte Carlo predictions were accurately reproduced for relaxivity-iron calibration. The predicted R Ã 2 and single spin echo R 2 increased by a factor of 2.00 and 1.51, respectively, at 1.5 versus 3.0 T. MSE signals and their corresponding R 2 depended strongly on LIC, interecho time, and field strength. Preliminary results showed that a nonmonoexponential model accurately characterizes the simulated MSE signals, and that strong correlations were found between predicted relaxation parameters and LIC. In conclusion, relaxivity-iron calibration is reproducible using the proposed Monte Carlo model. Furthermore, this model can be readily extended to other important applications, including predicting signal behavior for MSE imaging.