The purpose of this study was to determine classification criteria for herpes simplex virus (HSV) anterior uveitis DESIGN: Machine learning of cases with HSV anterior uveitis and 8 other anterior uveitides. Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated in the validation set. A total of 1,083 cases of anterior uveitides, including 101 cases of HSV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval: 92.4-98.6). Key criteria for HSV anterior uveitis included unilateral anterior uveitis with either 1) positive aqueous humor polymerase chain reaction assay for HSV; 2) sectoral iris atrophy in a patient ≤50 years old; or 3) HSV keratitis. The misclassification rates for HSV anterior uveitis were 8.3% in the training set and 17% in the validation set. The criteria for HSV anterior uveitis had a reasonably low misclassification rate and appeared to perform well enough for use in clinical and translational research.