After several decades of declining rates, maternal mortality climbed in California from a three-year moving average of 9.4 deaths per 100,000 live births in 1999–2001 to a high of 14.0 deaths per 100,000 live births in 2006–2008 (p < 0.001). The Maternal, Child and Adolescent Health Division of the California Department of Public Health developed a mixed method approach to identify and investigate maternal deaths to inform prevention strategies. This paper describes the methodology of the California Pregnancy-Associated Mortality Review (CA-PAMR) and its advantages for improved surveillance, cause of death analysis, and translation of findings. From 2002 to 2004, 1,598,792 live births occurred in California and 555 women died while pregnant or within one year of pregnancy. A screening algorithm identified cases for review that were likely to be pregnancy-related. Medical records were then abstracted and reviewed by a multidisciplinary committee to determine cause of death, contributing factors, and opportunities for quality improvement. Mixed methods were used to analyze, synthesize and translate Committee recommendations for improved care. Of 211 cases selected for review, 145 deaths were determined to be pregnancy-related. CA-PAMR methods corrected misclassification of cases and more accurately identified the leading causes of death. Cardiovascular disease emerged as the leading cause of pregnancy-related deaths (20 %), and African-American women were disproportionately represented among cardiovascular deaths. Overall, the chance to prevent the fatal outcome appeared good or strong in 40 % of cases reviewed. The CA-PAMR methodology resulted in additional case finding, improved accuracy of the causes of pregnancy-related deaths, and evidence to guide development of prevention and quality improvement efforts.