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Background: Preservatives are often necessary components of commercial products. Large-scale North American studies on preservative allergy are limited., Objective: To evaluate demographics, positive patch test reactions (PPTRs), clinical relevance, and trends for preservatives tested by the North American Contact Dermatitis Group., Methods: We conducted a retrospective cross-sectional analysis of North American Contact Dermatitis Group patch testing results of preservatives from 1994 through 2016., Results: A total of 50,799 patients were tested; 11,338 (22.3%) had a PPTR to at least 1 preservative. The most frequent reactions were to methylisothiazolinone 0.2% aqueous (aq) (12.2%), formaldehyde 2% aq (7.8%), formaldehyde 1% aq (7.8%), quaternium-15 2% petrolatum (pet) (7.7%), and methyldibromo glutaronitrile/phenoxyethanol 2% pet (5.1%). Paraben mix 12% pet (1%), iodopropynyl butylcarbamate 0.1% pet (0.4%), benzyl alcohol 1% pet (0.3%), and phenoxyethanol 1% pet (0.2%) had the lowest PPTRs. Linear regression analysis of preservatives tested showed that only methylchloroisothiazolinone/methylisothiazolinone 0.01% aq (parameter estimate, 0.42; 95% CI, 0.17-0.66; P < .005) had a significant increase in PPTRs over time., Limitations: Collected variables are dependent on clinical judgment. Results may be prone to referral selection bias., Conclusions: This large North American study provides insight on preservative PPTRs and trends from 1994 through 2016., (Copyright © 2020 American Academy of Dermatology, Inc. All rights reserved.)