Activated protein C resistance (APC-R) is the most common inherited defect of the coagulation system known to date, affecting 3–5% of Americans. It is an autosomal dominant disorder associated with an increased risk of venous thrombosis and is reportedly found in 21% of individuals with deep venous thrombosis. Medical examiners are in a unique position to make the diagnosis since a fatal pulmonary embolism may be the first manifestation of the disorder. This study examines the prevalence of APC-R in individuals who die suddenly of pulmonary embolism to help medical examiners decide if routine testing is indicated. We examined 66 cases of sudden death due to pulmonary embolism seen at the Bexar County Forensic Science Center in San Antonio, Texas, from 1993–1997. The median age was 46 years with a range of 14 to 93 years. Fifty-three percent were Caucasian, 24% were African-American, and 23% were Hispanic. Twenty-seven percent had no known risk factors for pulmonary embolism. Whole blood was tested for the factor V codon 506Q mutation responsible for APC-R using polymerase chain reaction. The prevalence of APC-R was 4.5%, which is similar to the prevalence of APC-R in the general American population. These data imply that individuals with APC-R are not at increased risk for sudden death due to pulmonary embolism. or, conversely, that most fatal pulmonary emboli seen in the medical examiner setting are not induced by APC-R. Routine postmortem testing for the factor V 506Q mutation does not appear indicated at this time, given the low prevalence and high cost of testing.