Introduction: Studies of pathology underlying sudden cardiac death (SCD) are biased by low autopsy rates or a focus on ischemic pathology. Leveraging the POST SCD Study, a countywide postmortem study of all presumed (WHO-defined) SCDs, we hypothesized that autopsy would identify contemporary substrates of SCD independent of coronary artery disease (CAD). Methods: We compared postmortem findings for presumed SCDs (97% autopsy rate including toxicology and vitreous chemistries) adjudicated as autopsy-defined sudden arrhythmic death (SAD, potentially rescuable with implantable cardioverter-defibrillator [ICD]) or non-SAD, and trauma death (TD) controls in San Francisco, California from 2/1/2011-3/1/2014. Heart weight Z-scores were based on 27,645 reference autopsies. Results: We evaluated 525 presumed SCDs (293 SADs; 232 non-SADs) and 104 TDs. Mean SAD heart weight was 1.34 standard deviations above expected (Z-score 1.34, Figure ), heavier (P<0.001) than non-SADs (Z-score 0.89) and TDs which closely matched expected weights (Z-score -0.02).Heart weight was heavier for SADs than non-SADs for cases without CAD (Z-score 1.4 vs. 0.7, P<0.001), but similar for cases with CAD. Chronic CAD was associated with higher risk of SAD (60% prevalence) than TD (14% prevalence; adjusted OR 7.0 [3.7-13.2], P<0.001); left anterior descending and right CAD conveyed highest risk. Adjusted for CAD, total fibrosis (replacement, interstitial) was higher for SADs (9.9 ± 8.0%) than non-SADs (7.5 ± 6%, P=0.018) and TDs (6.1 ± 5.8%, P=0.002). Compared to TDs, heart weight and total fibrosis were associated with SAD independent of CAD (P <0.05). Conclusion: In this 3-year study of autopsy-defined SAD, we identified chronic CAD, heart weight, and fibrosis as its pathologic substrates compared to prevalent cardiac pathology in the community. Since these factors can be assessed pre-mortem, they may be targets for contemporary risk stratification for SAD potentially rescuable with an ICD.