Diagnostic errors are common and have many contributing factors. This study analyzed more than 100 serious adverse event (SAE) reports in acute care using four investigation methods (e.g., Diagnostic Error Evaluation Research (DEER) taxonomy, Safer Dx Instrument) to identify common contributing factors. Transitions of care were particularly vulnerable to SAE, often due to incomplete communication between departments. Diagnostic errors occurred most often in the testing, assessment, and follow-up phases, with human factors as the most common contributing factor. Using multiple investigative methods supports more targeted interventions in each phase of diagnosis.