The introduction of positron emission/computed tomography (PET/CT) systems coupled with multidetector CT arrays has greatly increased the amount of clinical information in myocardial perfusion studies. The CT acquisition serves the dual role of providing high spatial anatomical detail and attenuation correction for PET. However, the differences between the interaction of respiratory and cardiac cycles in the CT and PET acquisitions presents a challenge when using the CT to determine PET attenuation correction. Three CT attenuation correction protocols were tested for their ability to produce accurate emission images: gated, a step mode acquisition covering the diastolic heart phase; normal, a high-pitch helical CT; and slow, a low-pitch, low-temporal-resolution helical CT. The amount of cardiac tissue in the emission image that overlaid lung tissue in the transmission image was used as the measure of mismatch between acquisitions. Phantom studies simulating misalignment of the heart between the transmission and emission sequences were used to correlate the amount of mismatch with the artificial defect changes in the emission image. Consecutive patients were studied prospectively with either paired gated (diastolic phase, 120 kVp, 280 mA, 2.6 s) and slow CT (0.562:1 pitch, 120 kVp, Auto-mA, 16 s) or paired normal (0.938:1 pitch, 120 kVp, Auto-mA, 4.8 s) and slow CT protocols, prior to a Rb-82 perfusion study. To determine the amount of mismatch, the transmission and emission images were converted to binary representations of attenuating tissue and cardiac tissue and overlaid using their native registration. The number of cardiac tissue pixels from the emission image present in the CT lung field yielded the magnitude of misalignment represented in terms of volume, of where a small volume indicates better registration. Acquiring a slow CT improved registration between the transmission and emission acquisitions compared to the gated and normal CT protocols. The volume of PET cardiac tissue in the CT lung field was significantly lower (p < 0.03) for the slow CT protocol in both the rest and stress emission studies. Phantom studies showed that an overlaying volume greater than 2.6 mL would produce significant artificial defects as determined by a quantitative software package that employs a normal database. The percentage of patient studies with overlaying volume greater than 2.6 mL was reduced from 71% with the normal CT protocol to 28% with the slow CT protocol. The remaining 28% exhibited artifacts consistent with heart drift and patient motion that could not be corrected by adjusting the CT acquisition protocol. The low pitch of the slow CT protocol provided the best match to the emission study and is recommended for attenuation correction in cardiac PET/CT studies. Further reduction in artifacts arising from cardiac drift is required and warrants an image registration solution.