Coated activated charcoal hemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomised clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared to standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes following AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control group were found when analysing for differences in AT levels in plasma at any time point. Furthermore, significant differences between the control and intervention group in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared to standard treatment alone. We hypothesize that the effect of modern CAC-HP as a treatment modality in AT poisoned human patients may be inadequate. This article is protected by copyright. All rights reserved.