Coated activated charcoal haemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomized, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035-0.297, p-values 0.421-0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time-plus-group level of significance revealed a p-value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.