Purpose: To determine the demographic and social characteristics of acutely intoxicated patients in the emergency department (ED), intention of drug/chemical intake, main toxic agents, outcomes and time trends for all variables., Methods: This prospective, observational study included acutely intoxicated patients treated in the ED of the University Hospital Centre Sisters of Charity, Zagreb, Croatia, during the years 2001, 2010 and 2015. The diagnosis was derived from patient's self-report, clinical observations and laboratory test results (quantitative test for serum ethanol levels and qualitative tests for drugs in urine)., Results: A total of 1593 patients were enrolled in the study (331 in 2001, 618 in 2010, 644 in 2015), with a predominance of men (55.9%, 65.2%, 70.7%, respectively). The median age was 28 [18-89], 39 [18-92] and 40 years [18-95], respectively. There was a decline in the number of suicide attempts during the study (46.2%, 22.2%, 17.1% of patients, respectively) with a predominance of women (64.1-68.2%), and an escalation in the number of unintentional overdoses by substances of abuse (50.2%, 72.3%, 81.7% of patients, respectively) with a predominance of men (74.1-79.1%). Ethanol was the main toxic agent (40.2%, 69.4%, 75.8% of patients, respectively), used primarily as a substance of unintentional overdose. Anxiolytics were the most frequently implicated pharmaceuticals among all patients (46.5%, 32.0%, 18.5% of patients, respectively) and the main substance used in suicide attempts. The number of patients hospitalized in the Intensive Care Unit (ICU) decreased during the study from 20.2% of all patients in 2001 to 7.9% in 2010 and 6.8% in 2015. They accounted for 7.2%, 5.8% and 5.6% of all ICU-treated patients, respectively. In-hospital mortality (ED and ICU) caused by acute intoxications was low (0.9%, 0.8%, 0.8%, respectively)., Conclusions: The escalation of overdoses by ethanol was a major medical and public concern in Zagreb. Anxiolytics were the main substance used in suicide attempts, with a low death rate due to their good safety profile.