Maternal mortality rates rose markedly from 2002 to 2006 in California, prompting an in-depth maternal mortality review in a state which comprises one twelfth of the U.S. birth cohort. Cardiovascular disease has emerged as the leading cause of pregnancy-related deaths in the U.S. This study found that African-American race, substance use, and obesity were risk factors for pregnancy-related cardiovascular disease mortality. Chronic disease prevention and better recognition and response to cardiovascular disease during pregnancy are needed to reduce maternal mortality.