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Background. Skin contact with items containing p-tert-butylphenol-formaldehyde resin (PTBP-FR) may induce sensitization and allergic contact dermatitis (ACD). Methods. This multi-centric cross-sectional study investigated the prevalence of sensitization to PTBP-FR in 30,629 consecutive outpatients patch-tested during 1997–2021 in four research centers from Northern Italy: Padua; Pordenone; Trieste; and Trento/Bolzano/Rovigo. Patch tests were applied on the upper back of patients with suspected ACD. All patches were removed after 48 h and read at 72 or 96 h. Results. The overall prevalence of PTBP-FR sensitization was 1.11% (=341/30,629) of cases, with lower prevalence occurring in the Province of Trento/Bolzano/Rovigo (0.36%). The body area most frequently affected were the hands (36.32%), followed by face (19.52%) and legs (8.09%). During 1997–2004, the prevalence of PTBP-FR positivity was significantly lower in Trento/Bolzano/Rovigo (aOR = 0.19; 95%CI: 0.11; 0.35), whereas it was higher among restaurant workers (aOR = 2.44; 95%CI: 1.44; 4.13). During the entire study period (1997–2021), excluding Trento/Bolzano/Rovigo, PTBP-FR positivity significantly decreased in the period 2011–2021 (aOR = 052; 95%CI: 0.39; 0.69) compared to 1997–2010 in males (OR = 0.69; 95%CI: 0.52; 0.91). Conclusions. Females were likely to react to PTBP-FR at patch tests. Prevalence of PTBP-FR sensitization significantly decreased over time, possibly reflecting reduced occupational and non-occupational exposure due to replacement of the resin with other adhesive products (acrylates or epoxy agents). Full article