Background: Diagnostic errors, reframed as missed opportunities for improving diagnosis (MOIDs), in pediatric emergency departments (EDs) are poorly understood. We investigated the epidemiology, harm, and contributing factors related to MOIDs self-reported by ED physicians participating in the Pediatric Emergency Research Networks (PERN). Methods: We developed a two-part, web-based survey. In Part 1, physicians described examples of MOIDs involving their own patient or a colleague’s patient. Respondents provided a brief summary and answered questions regarding harm and factors contributing to the event (process dimensions of the Safer Dx framework). In Part 2, physicians provided perspectives related to enhancing the understanding of diagnostic safety in pediatric EDs. Results: Of 1594 physicians, 412 (25.8%) responded (M age = 43 years [SD=9.3], 58% female, mean years in practice = 12 [SD=9.0]). Patient presentations involving MOIDs had common undifferentiated symptoms, including abdominal pain, headache, and fever. Often, affected patients were discharged from the ED with commonly occurring diagnoses (e.g. constipation, bronchiolitis, asthma, viral infections). Most reported MOIDs (65%) detected on ED return visits (46% within 24 hours and 76% within 72 hours). Often, the correct diagnoses included life-threatening conditions (e.g. myocarditis, cancer, physical abuse, meningitis). 93% reported a clear opportunity to make the correct diagnosis at initial ED encounter. Reported contributing factors: patient-provider encounter (61%), diagnostic tests (40%), patient-related factors (28%), follow-up (14%) and consultations (10%). More than half (54%) of the reported MOIDs involved the patient-provider encounter, with misinterpreted/ignored history or an incomplete/inadequate physical examination. More than half of patients had moderate (49%) or major (10%) harm. Respondents most commonly reported MOIDs associated with medical presentations (86%), followed by surgical (11%) and trauma (3%). Nearly half (46%) witnessed a MOID 1-2 times per month. MOIDs associated with patient harm were noted by 65% at a frequency of 1-2 times per year. Nearly half (41%) reported fear of open discussion of MOIDs. More than half (56%) felt patients received unnecessary diagnostic tests in the ED and 42% felt patients suffered harm from over-testing than from delayed/missed diagnosis. However, 46% suggested they rather over-test than accept diagnostic uncertainty at time of the patient encounter. A majority (80%) suggested ongoing training in clinical reasoning should be an important part of continuing education. Conclusions: In a global cohort, one in five pediatric ED physicians reported a patient experiencing a diagnostic error. Our study suggests that errors occur in children who present with common complaints and errors share common contributory factors across practice settings and countries. Physicians’ personal experiences offer an under-explored source for investigating and mitigating diagnostic error. Despite recognizing the use of unnecessary diagnostic tests, several preferred over-testing than diagnostic uncertainty. Advancement of clinical reasoning skills should also target the balance between diagnostic uncertainty and over-testing.