Migrant studies in the United States (US) have rarely covered the Middle Eastern population (ME), and have never distinguished the first and second generations born in the US. This study aims to describe the mortality patterns of ME immigrants by origin, acculturation, and generation. Death certificates issued from 1997 through 2004 were used to calculate, for Middle Eastern immigrants, the proportional odds ratios (POR) for major causes of death, with comparison to non-Hispanic Whites born in the US to US-born parents. First generation immigrants had higher odds for colorectal cancers, diabetes, and diseases of the heart, while their odds for chronic obstructive pulmonary disease (COPD) and suicide were lower. Men had higher odds for all cancers combined, cancers of the lymphatics, and pancreas. Women had lower odds for lung cancer, and dementia, and higher odds for breast cancer. The second generation men had higher odds for all cancers combined, and diseases of the heart, whereas women had lower odds for lung cancer and cerebrovascular accidents. Higher odds for colorectal cancers and lower odds for COPD were noted in both sexes. Some of the observed differences may be based on ethnic characteristics, including genetic makeup, early exposures, and culturally determined values. Time since immigration is associated with convergence of most odds to that of the native population.