In this paper, we apply the channelized Hotelling observer (CHO) using a defect detection task to the optimization and evaluation of three-dimensional iterative reconstruction-based compensation methods for myocardial perfusion single-photon emission computed tomography (SPECT). We used a population of 24 mathematical cardiac-torso phantoms that realistically model the activity and attenuation distribution in three classes of patients: females, and males with flat diaphragms and raised diaphragms. Projection data were generated and subsequently reconstructed using methods based on the ordered subsets-expectation maximization (OSEM) algorithm. The methods evaluated included compensation for attenuation, detector response blurring, and scatter in various combinations. We applied the CHO to optimize the number of iterations for OSEM and the cutoff frequency and order of a three-dimensional postreconstruction Butterworth filter. Using the optimal parameters, we then compared the compensation methods. The index of comparison in these studies was the area under the receiver operating characteristics curve (AUC) for the CHO. We found that attenuation compensation with either detector response or scatter compensation gave statistically significant increases in the AUC compared to attenuation compensation alone. The greatest increase in the AUC occurred when all three compensations were applied. These results indicate that compensation for detector response and scatter, in addition to attenuation compensation, will improve defect detectability in myocardial SPECT images.