Overdoses of tricyclic antidepressants may lead to arrhythmia. The aim of the study was to simulate the effect of increasing concentrations of amitriptyline (AMI) and its metabolite, nortriptyline, on the action potential of human ventricular cell. Methods: Simulations were performed in Cardiac Safety Simulator platform with the use of the O’Hara-Rudy model. Input data included literature-derived, drug-specific IC50 values for ICa(L), IKr, and INa currents. Individual concentrations of AMI and nortriptyline were simulated in Simcyp. Nine single doses (mg) were tested: 5, 10, 50, 100, 300, 500, 1000, 5000, and 10,000. Results: The values of simulated endpoints (APD50, APD90, triangulation, and APD90) increase with drug concentrations. APD90 was statistically significant for doses up from 1000 mg. EADs were observed after administration of 10,000-mg AMI. Conclusions: The consequences of various doses of AMI on the single cardiac myocytes were simulated in our study. Repolarization abnormalities were not expected for the therapeutic doses. EADs may be observed for very high doses of AMI.