Objective: The objective of this study was to assess predictors of emergency department (ED) ketamine-associated laryngospasm using case-control techniques. Methods: We performed a matched case-control analysis of a sample of 8282 ED ketamine sedations (including 22 occurrences of laryngospasm) assembled from 32 prior published series. We sequentially studied the association of each of 7 clinical variables with laryngospasm by assigning 4 controls to each case while matching for the remaining 6 variables. We then used univariate statistics and conditional logistic regression to analyze the matched sets. Results: We found no statistical association of age, dose, oropharyngeal procedure, underlying physical illness, route, or coadministered anticholinergics with laryngospasm. Coadministered benzodiazepines showed a borderline association in the multivariate but not univariate analysis that was considered anomalous. Conclusions: This case-control analysis of the largest available sample of ED ketamine-associated laryngospasm did not demonstrate evidence of association with age, dose, or other clinical factors. Such laryngospasm seems to be idiosyncratic, and accordingly, clinicians administering ketamine must be prepared for its rapid identification and management. Given no evidence that they decrease the risk of laryngospasm, coadministered anticholinergics seem unnecessary.