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Objective: This study investigated South Asians' explanatory models (EM) of CHD and compared them to the biomedical model as part of an effort to inform the development of culturally targeted CHD prevention messages., Methods: We conducted in-depth, semi-structured interviews in English, Hindi and Urdu with 75 respondents from a federally qualified health center and at a community center for South Asian immigrants in Chicago, Illinois., Results: While EMs of CHD included risk factors from the biomedical model, they also included psychosocial and spiritual risk factors. Respondents emphasized that stress causes CHD and suggested that CHD was caused by sudden or inexplicable factors. Few respondents discussed cholesterol, blood pressure, or diabetes as part of CHD prevention. Women and those with lower education had low perceptions of being at-risk for CHD., Conclusion: South Asians' EMs of CHD encompassed the biomedical model; however, EMs also included psychosocial and spiritual factors., Practice Implications: Clinicians and health educators should be aware that South Asian individual's EM of CHD may include psychosocial and spiritual factors which can affect CHD prevention behaviors., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)