Abstract Objective To perform long QT syndrome and catecholaminergic polymorphic ventricular tachycardia cardiac channel postmortem genetic testing (molecular autopsy) for a large cohort of cases of autopsy-negative sudden unexplained death (SUD). Methods From September 1, 1998, through October 31, 2010, 173 cases of SUD (106 males; mean ± SD age, 18.4±12.9 years; age range, 1-69 years; 89% white) were referred by medical examiners or coroners for a cardiac channel molecular autopsy. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, a comprehensive mutational analysis of the long QT syndrome susceptibility genes ( KCNQ1 , KCNH2 , SCN5A, KCNE1, and KCNE2 ) and a targeted analysis of the catecholaminergic polymorphic ventricular tachycardia type 1–associated gene ( RYR2 ) were conducted. Results Overall, 45 putative pathogenic mutations absent in 400 to 700 controls were identified in 45 autopsy-negative SUD cases (26.0%). Females had a higher yield (26/67 38.8%) than males (19/106 17.9%; P <.005). Among SUD cases with exercise-induced death, the yield trended higher among the 1- to 10-year-olds (8/12 66.7%) compared with the 11- to 20-year-olds (4/27 14.8%; P =.002). In contrast, for those who died during a period of sleep, the 11- to 20-year-olds had a higher yield (9/25 36.0%) than the 1- to 10-year-olds (1/24 4.2%; P =.01). Conclusion Cardiac channel molecular autopsy should be considered in the evaluation of autopsy-negative SUD. Several interesting genotype-phenotype observations may provide insight into the expected yields of postmortem genetic testing for SUD and assist in selecting cases with the greatest potential for mutation discovery and directing genetic testing efforts.