Amitriptyline is a very frequently prescribed antidepressant agent and is very often involved in attempted suicides. Amitriptyline intoxication necessitates primary therapeutic approaches that include gastric irrigation and recurrent administration of activated charcoal. In the case of pronounced anticholinergic findings, physostigmine is of proven benefit and hypertonic sodium bicarbonate can be used to shorten the QRS duration and AV interval. In cases of a comatosed state, hemoperfusion and plasma exchange can be used. In this case report we present a case of severe amitriptyline poisoning that we successfully managed with plasma exchange. We confirmed a 59.5% reduction in the amitriptyline plasma level in our patient after a single plasma exchange session. She was discharged by the third day of admission without any complications. According to current literature, our patient is the fifth patient treated with plasma exchange to be the subject of a publication.