The first-generation antihistamine, promethazine, became a prescription-only drug in Denmark as of December 2014. First-generation antihistamines are known to have a higher toxic potential than second-generation antihistamines. The aim of this study was to provide a nationwide description of the antihistamine use and poisoning pattern from 2007 to 2013 in Denmark based on two independent databases. There were 1049 antihistamine exposures in the national, advisory telephone service specialized in poisonings, the Danish Poison and Information Centre (DPIC), and 456 exposures in the three registers used within the State Serum Institute of Denmark (SSI), a department under the Danish Ministry of Health dealing with research-based health surveillance in Denmark. First-generation antihistamines constitute 61% and 73% of antihistamine registrations in DPIC and SSI, respectively. Antihistamine exposures increased by 7 exposures/10,000 enquiries per year in DPIC and six admissions per year in SSI -this increase is not significant due to a sudden decrease in 2012. Intentional exposures constituted 65% in DPIC of which 82% was due to suicide attempts, and 78% of the involved antihistamines were first-generation antihistamines. Accidental exposures constituted 33% of which 61% were due to play and 29% involved first-generation antihistamines. Single antihistamine exposures constituted 65% of DPIC exposures of which 98% involved only one brand of antihistamine. Multidrug exposures constituted 35% of DPIC exposures with equally distributed coingestants. Hospitalization was recommended in 78% of DPIC exposures. Admissions required only 1-day of treatment in 91% of the SSI exposures. One of the 14 identified deaths in the SSI study population was directly related to antihistamine poisoning. Results support the limited disclosure of promethazine in Denmark and illustrate a generation-specific pattern indicating a suspected replacement of promethazine with other firstgeneration antihistamines.