The aim of this study is to compare acute toxicity of fluoxetine versus that of amitriptyline among patients admitted to the Poison Control Centre, Ain Shams University (PCC-ASU) and to investigate some predictive factors for the development of complications in such cases. METHODS: A prospective study was conducted in the PCC-ASU during the period between January 2013 and December 2015. The study included 31 patients ingested fluoxetine alone and 49 patients ingested amitriptyline alone. Parameters: Descriptive variables: (age, gender, amount taken, delay time and manner of poisoning). Clinical variables: Vital signs, mean QRS duration, corrected QT (QTc), cardiac arrhythmias ,level of consciousness (assessed by Glasgow coma scale (GCS), pupil size and reactivity, seizures and symptoms of serotonin toxicity. Laboratory variables: (Serum sodium, potassium, calcium and magnesium and blood glucose level).The outcome variables: percentage of cases with: cardiac arrhythmias, QRS ≥100,QTc ≥440, seizures, GCS ≤10, serotonin toxicity, ICU admission, length of stay in ICU, length of hospital stay and survival. RESULTS: there was highly significant increase of the age, amount of drug ingested, mean QRS, QTc, mydriasis and significant decrease in the mean GCS and serum sodium in amitriptyline group compared to fluoxetine group. A highly significant increase of percentage of tremors, clonus, hyper-reflexia and diaphoresis was observed in fluoxetine group. As regards outcome variables, there was insignificant difference in percentage of cases with seizures and survival between both groups. There was significant increase in percentage of cases with QRS ≥100, QTc ≥440, GCS ≤10, ICU admission, length of stay in ICU and hospital in amitriptyline group. There was a highly significant increase of cases with serotonin toxicity in fluoxetine group.The patients who developed seizures after acute amitriptyline toxicity, showed a highly significant increase in the amount of drug intake, QRS, QTc duration and length of hospital stay and highly significant decrease of mean GCS and serum sodium level compared with patients without seizures. By applying logistic regression analysis, QRS ≥100 and QTc≥440 interval and  GCS ≤10 were identified as independent risk factors and QRS≥100 showed (sensitivity 97%, specificity 71%, PPV 67% and NPV 97%);  QTc ≥440 interval showed (sensitivity 65%,specificity 64%, PPV55% and NPV 68%) and GCS ≤10 showed (sensitivity 86%, specificity 71%, PPV 60% and NPV 80%).The patients who developed seizure after acute fluoxetine toxicity showed a highly significant increase in the amount of drug intake, QTc duration, and percentage of cases with serotonin toxicity and length of hospital stay and highly significant decrease of mean GCS compared with patients without seizures. By applying logistic regression analysis, QTc≥440, GCS≤10, and serotonin toxicitywere identified as independent risk factors. QTc interval ≥440 showed (sensitivity 62%, specificity 82%, PPV 55% and NPV 86%); GCS≤10 showed (sensitivity 72%, specificity 84%, PPV 60% and NPV 91%) and serotonin toxicity showed (sensitivity 100%, specificity 86%, PPV72% and NPV 100%). IN CONCLUSION: Fluoxetine intoxicated patients encountered complications as serotonin toxicity and seizure in acute large doses and the predictive risk factors for seizure were QTc ≥440, GCS ≤10 and serotonin toxicity. Amitriptyline intoxication associated with seizures and the predictive risk factors for seizure were QRS ≥100 and QTc ≥440 and GCS ≤10.