BACKGROUND: Incidence, risk factors, and perinatal morbidity and mortality rates related to amniotic fluid embolism remain a challenge to evaluate, given the presence of differing international diagnostic criteria, the lack of a gold standard diagnostic test, and a significant overlap with other causes of obstetric morbidity and mortality. OBJECTIVE: The aims of this study were (1) to analyze the clinical features and outcomes of women using the largest United States-based contemporary international amniotic fluid embolism registry, and (2) to investigate differences in demographic and obstetric variables, clinical presentation, and outcomes between women with typical versus atypical amniotic fluid embolism, using previously published and validated criteria for the research reporting of amniotic fluid embolism. MATERIALS AND METHODS: The AFE Registry is an international database established at Baylor College of Medicine (Houston, TX) in partnership with the Amniotic Fluid Embolism Foundation (Vista, CA) and the Perinatology Research Branch of the Division of Intramural Research of the NICHD/NIH/DHHS (Detroit, MI). Charts submitted to the registry between August 2013 and September 2017 were reviewed, and cases were categorized into typical, atypical, non-amniotic fluid embolism, and indeterminate, using the previously published and validated criteria for the research reporting of AFE. Demographic and clinical variables, as well as outcomes for patients with typical and atypical AFE, were recorded and compared. Student t tests, χ tests, and analysis of variance tables were used to compare the groups, as appropriate, using SAS/STAT software, version 9.4. RESULTS: A total of 129 charts were available for review. Of these, 46% (59/129) represented typical amniotic fluid embolism and 12% (15/129) atypical amniotic fluid embolism, 21% (27/129) were non-amniotic fluid embolism cases with a clear alternative diagnosis, and 22% (28/129) had an uncertain diagnosis. Of the 27 women misclassified as an amniotic fluid embolism with an alternative diagnosis, the most common actual diagnosis was hypovolemic shock secondary to postpartum hemorrhage. Ten percent (6/59) of the women with typical amniotic fluid embolism had a pregnancy complicated by placenta previa, and 8% (5/61) had undergone in vitro fertilization to achieve pregnancy. In all, 66% (49/74) of the women with amniotic fluid embolism reported a history of atopy or latex, medication, or food allergy, compared to 34% of the obstetric population delivered at our hospital over the study period (P < .05). CONCLUSION: Our data represent a series of women with amniotic fluid embolism whose diagnosis has been validated by detailed chart review, using recently published and validated criteria for research reporting of amniotic fluid embolism. Although no definitive risk factors were identified, a high rate of placenta previa, reported allergy, and conceptions achieved through in vitro fertilization was observed.