A ROC study was performed in order to evaluate whether the maximum likelihood expectation maximization (ML-EM) reconstruction algorithm improves diagnostic performance compared to the conventional filtered backprojection method in SPECT. Several implementations of the algorithm were tested including 25 and 50 iteration stopping points, with and without nonuniform attenuation compensation, and with and without Metz filtering. Filtered backprojection was with Metz filter and without attenuation compensation. The test data were computer simulated to model cardiac 201Tl SPECT. The data incorporated the effects of nonuniform attenuation, distance-dependent collimator response, and scatter. Patient CT images provided realistic anatomy and attenuation information for the data simulation. Four observers each viewed 120 images for each of the reconstruction methods. Lesion detectability with ML-EM increased with Metz filtering and decreased with nonuniform attenuation compensation. The best MIL-EM implementation, 50 iterations with Metz filtering and without attenuation compensation, was not statistically better than filtered backprojection.