BACKGROUND Soft-tissue attenuation remains a major limitation of SPECT-MPI which interferes with the diagnosis of CAD. The current study aims to evaluate the pattern of attenuation artifacts in supine and semi-reclining positions on CZT cardiac camera and their interaction with gender, BMI and stress protocols. METHODS We prospectively analysed 150 patients acquired in supine and semi-reclining positions on CZT camera. The images were evaluated for severity and extent of defect using 17-segment model. An additional CT scan was acquired to generate AC image in the first 50 patients studied to assist investigator learning for comparison of artifact vs true defects in the two SPECT systems. The defects present in one position or showing change in severity within two positions were considered as positional artifacts and further validated using CTAC supine image. RESULTS In overall analysis, higher extent and severity of positional artifacts were observed more in semi-reclining position affecting the apex, apico-inferior, inferolateral and inferoseptal segments. Females showed more positional artifacts than males with inferior wall attenuation in the semireclining position and anterior wall attenuation in the supine position. A positive correlation of the extent and severity of positional artifacts was noted with an increasing BMI. In patients with BMI > 30, mid inferior and inferolateral segments were most affected followed by anterior wall segments. Highest correction of artifactual perfusion defects by CTAC was noted in inferior wall followed by inferolateral segments. CONCLUSIONS The incidence of positional artifacts was greater in semi-reclining position in females, higher BMI groups and adenosine stress subsets. Knowledge of the pattern of positional artifacts appears to be a reliable alternative of CTAC for correct interpretation of myocardial perfusion images.