Background:Intentional drug overdose (IDO) is the most common form of hospital-treated self-harm, yet no national study has systematically classified the range of drugs involved using a validated system. We aimed to determine the profile of patients engaging in overdose, to identify drugs frequently used and to quantify the contributions of multiple drug use and alcohol involvement. Methods: Between 2012 and 2014, the National Self-Harm Registry, Ireland recorded 18 329 presentations of non-fatal IDO to Irish emergency departments. Information on demographic and overdose characteristics were obtained. Drugs were categorized using the Anatomical Therapeutic Chemical classification system. Results: Analgesics (32.4%), antidepressants (21.9%), anxiolytics (21.2%) and hypnotics and sedatives (21.0%) were the most frequently used drugs types involved in overdose. Presentations involving analgesic and antidepressant medication were more common for females whereas males more often took illegal, anxiolytic and hypnotic and sedative drugs. Overdoses with drugs other than those which affect the nervous system were identified, including musculoskeletal drugs, taken in 12.0% of presentations. Paracetamol was the most frequently used drug, particularly among females (32.0%) and persons under 25 years (36.2%). Alcohol was most often present in overdoses involving anxiolytics and illegal drugs. Multiple drug use was a factor in almost half (47.1%) of presentations. Conclusions: People who engage in IDO frequently take prescription only or sales restricted drugs, often involving alcohol and/or multiple drug use. These findings highlight the importance of addressing drug and alcohol misuse, potential inappropriate prescribing and the enforcement of legislation restricting specific drug sales.