Simultaneous acquisition of 99mTc stress and 201Tl rest myocardial perfusion SPECT has several potential advantages, but the image quality is degraded by cross-talk between the Tc and Tl data. We have previously developed down-scatter and Pb X-ray models for cross-talk compensation. In this work, we validated these models by comparing the crosstalk from 99Tc to the Tl window calculated using our models with the cross-talk simulated using a combination of the SimSET-MCNP Monte Carlo simulation codes. We have also evaluated the model-based cross-talk compensation method using both simulated data from MCAT phantoms and experimental data from a physical phantom with a myocardial defect. In the studies the Tl distributions were reconstructed from cross-talk contaminated data without cross-talk compensation, with compensation using the model-calculated cross-talk or using the true cross-talk, and were compared with that from uncontaminated Tl data. Results show that the models gave good estimates of both the down-scatter photons and Pb X-rays in the simultaneous dual isotopes myocardial perfusion SPECT. Also, the results show that model-based cross-talk compensation method provided image quality significantly improved as compared to no compensation and very close to that from the separate acquisition.