The purpose of this study was to evaluate the patients with acute amitriptyline poisoning and investigate predictive factors for the development of life-threatening complications. Demographics, clinical, laboratory, and electrocardiographic (ECG) findings of 250 patients were evaluated retrospectively. Predictive parameters for the development of serious complications were studied. Median age of patients was 14.6 years, of which, 70% of patients were female and 66% were in pediatric age group. The most common pathological clinical finding and laboratory abnormality were alteration of consciousness and hyponatremia. The rate of convulsive seizure, arrhythmia, and respiratory depression were 17 (6.8%), 16 (6.4%), and 11 (4.4%), respectively. These complications were more seen in pediatric patients than adults (15.8% and 1.2%). The incidence of hyponatremia was more in pediatric patients and severe poisoning groups (38.8 and 53.4%, respectively). The levels of amitriptyline and nortriptyline were significantly higher in the group with complications than the group without complications (p < 0.05). All adult patients were discharged with good prognosis. In pediatric age group, one patient was discharged with severe neurological sequelae and one patient died. QRS duration >100 ms, long corrected QT duration interval, and low Glasgow Coma Score (GCS) at admission were identified as independent risk factors for the development of life-threatening complications (odds ratio: 69.4, 1.9, and 1383, respectively; p < 0.05). Amitriptyline poisoning may be associated with life-threatening complications, especially in pediatric age group and in patients with hyponatremia. Low GCS, presence of hyponatremia, high serum drug levels, and pathological ECG findings on admission may be helpful in predicting the development of complications and poor prognosis.