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To describe trends in abuse, misuse, and suicide attempts involving diphenhydramine (DPH). We analyzed intentional DPH exposures of individuals ≥10 years old reported to U.S. Poison Control Centers using data from the National Poison Data System, 2005-2016. There were 158,774 intentional DPH exposures in our dataset. The rate of intentional exposures increased 63% over the 12-year study period for all ages combined. Suicide attempts involving DPH showed a bimodal distribution-increasing 263% among children 10-14 years of age, and 126 and 143%