BackgroundMissed vascular events, infections, and cancers account for ~75% of serious harms from diagnostic errors. Just 15 diseases from these “Big Three” categories account for nearly half of all serious misdiagnosis-related harms in malpractice claims. As part of a larger project estimating total US burden of serious misdiagnosis-related harms, we performed a focused literature review to measure diagnostic error and harm rates for these 15 conditions.MethodsWe searched PubMed, Google, and cited references. For errors, we selected high-quality, modern, US-based studies, if available, and best available evidence otherwise. For harms, we used literature-based estimates of the generic (disease-agnostic) rate of serious harms (morbidity/mortality) per diagnostic error and applied claims-based severity weights to construct disease-specific rates. Results were validated via expert review and comparison to prior literature that used different methods. We used Monte Carlo analysis to construct probabilistic plausible ranges (PPRs) around estimates.ResultsRates for the 15 diseases were drawn from 28 published studies representing 91,755 patients. Diagnostic error (false negative) rates ranged from 2.2% (myocardial infarction) to 62.1% (spinal abscess), with a median of 13.6% [interquartile range (IQR) 9.2–24.7] and an aggregate mean of 9.7% (PPR 8.2–12.3). Serious misdiagnosis-related harm rates per incident disease case ranged from 1.2% (myocardial infarction) to 35.6% (spinal abscess), with a median of 5.5% (IQR 4.6–13.6) and an aggregate mean of 5.2% (PPR 4.5–6.7). Rates were considered face valid by domain experts and consistent with prior literature reports.ConclusionsDiagnostic improvement initiatives should focus on dangerous conditions with higher diagnostic error and misdiagnosis-related harm rates.