BackgroundPatch testing to multiple cross reactive allergens for allergic contact dermatitis (ACD) may not be necessary due to copositivity. ObjectiveWe evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test. MethodsA retrospective analysis of Mayo Clinic (1997-2022) examined the well-established copositive formaldehyde group: Formaldehyde, Quaternium 15, Hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, Diazolidinyl urea, Imidazolidinyl urea, Toluenesulphonamide formaldehyde resin, DMDM hydantoin, and Ethyleneurea melamine formaldehyde mix. Patch Optimization Platform (POP) identified which single formaldehyde-related allergen optimally captures patients with clinically relevant ACD. Next, POP determined the optimal additional 1, 2, 3, etc. allergens. Cost per patch test was $5.19 (Medicare 2022). Results9832 patients were tested to all listed allergens, with 830 having positive patch tests. POP determined that Quaternium 15 alone captures 53% of patients with ACD to the formaldehyde group; adding the optimal second allergen (Formaldehyde 1%) captures 78%; the optimal five top allergens capture over 94% of patients. The incremental cost-per-additional-diagnosis increased up to 44-fold as the number of allergens tested increased. LimitationsData is from a single institution, and the cost-per-test was fixed to Medicare Part B in 2022. ConclusionsFor diagnosing ACD, we recommend considering an optimized allergen selection algorithm.