BACKGROUND: Methyldibromoglutaronitrile/phenoxyethanol (MDBGN/PE) is a broad-spectrum preservative mixture used in consumer and industrial products. OBJECTIVES: The aims of the study were (1) to characterize the prevalence and clinical relevance of patch test reactions to MDBGN/PE and the epidemiology of positive patients and (2) to determine the frequency of concomitant reactions of MDBGN/PE and its components. METHODS: This study used a retrospective analysis of cross-sectional data compiled by the North American Contact Dermatitis Group from 1994 to 2018. RESULTS: Of 55,477 tested patients, 2674 (4.8%) had positive patch test reactions to MDBGN/PE (1.0%-2.5% petrolatum [pet]); most were + (63.3%) or ++ (22.3%). Clinical relevance was considered definite in 3.0% and probable in 19.3% of reactions. Common dermatitis sites included the hands (26.4%), scattered/generalized distribution (24.7%), and the face (18.3%). Patients with a positive reaction to MDBGN/PE and/or MDBGN and/or PE were significantly more likely to be male and older than 40 years and/or had hand dermatitis (P ≤ 0.0033). Positivity to MDBGN/PE 2.0% pet decreased significantly over time (from 6.0% in 1998-2000 to 2.5% in 2017-2018, P < 0.0001). Personal care products were the most common exposure source (53.2%). CONCLUSIONS: Over time, positivity to MDBGN/PE 2.0% pet decreased significantly from 6.0% (in 1998-2000) to 2.5% (in 2017-2018). The high proportion of weak (63.3%) reactions underscore the need for careful interpretation of patch test sites. Important demographic associations included male sex and age older than 40 years.