Given the incidence and severity of acute intoxication, this issue is of considerable importance today for the Emergency Departments (ED). The objective of this study was to evaluate acute intoxications by psychopharmacological medications and abuse of drugs for patients managed in an Outpatient Emergency Department. Retrospective analyses were performed on data on admissions to the Emergency Department for the years 2012 and 2013, in Holy Trinity Hospital, Cagliari, Italy; the reference population were outpatients with intoxication reported as the main problem, taken from a total population of outpatients with every kind of medical problem admitted to the ED during the studied period. The sample included patients of all ages with acute intoxication by psychopharmacological medications and drugs of abuse (psychoactive drugs and alcohol). For the year 2012, the number of total Emergency Room (ER) visits because of intoxication amounted to 338 and 243 of these were due to the abuse of drugs (72%), representing 0.72% of the total number of ER outpatients visits (n=33823). For the year 2013, this percentage increased reporting 287 outpatients for intoxication by drugs of abuse (79% of those admitted because of intoxication, n=362), representing 0.83% of the total number of ER outpatients visits (n=34,476). If we consider jointly outpatients with intoxication because of drug abuse for the two years (n=530), the descriptive analysis shows that: 56.0% are male and 44.0% females. Yellow as priority code had been assigned in 67.7% cases and red in 9.2% cases (χ2=10.053, df=3, p=0.018). Patients with a diagnosis of psychiatric illness were 40.8%; with diagnosis of drug addiction 18.5%, 10.9% alcoholism, drug addiction and alcoholism 2.6%; psychiatric condition associated with drug addiction and/or alcoholism 4.5% (χ2=85.697, df=7, p<0.001). The drugs taken were: psychopharmacological medications 46.2%; alcohol 22.6%; mixed drugs and alcohol abuse 13.7% (χ2=104.870, df=8, p<0.001). This study showed that there is a high level of comorbidity between psychiatric disease (Bipolar Disorders: 28.7%, Unipolar Mood Disorders: 48.6%, Psychosis: 9.3%, Anxiety Disorders: 10.2%)  and acute intoxication in patients who are admitted to an Emergency Department; this data, which show an increase of admissions of such patients during the examined period prove the necessity to reflect on the importance of an appropriate management of this patient population.