Background. Acetylcysteine (ACC) is an effective antidote for paracetamol poisoning. There are various schemes for its application. At the same time, there is currently no information about the most priority of them in this pathology. Few studies indicate the effectiveness of the 12-hour protocol for ACC administration in paracetamol poisoning. However, there were not enough justifications for the introduction of a modified 12-hour scheme into world practice.The objective was to compare the effectiveness of the 12-hour and 21-hour protocols for the administration of acetylcysteine in paracetamol poisoning.Materials and methods. 43 patients with acute paracetamol poisoning were examined. The study group (prospective) consisted of 23 patients who underwent the 12-hour ACC protocol; the comparison group (retrospective) with the 21-hour ACC protocol included 20 patients. Groups were comparable. The endpoints were: ALT blood level, the frequency of allergic reactions, the duration of treatment in the ICU, the duration of stay in the hospital.Results. The 12-hour and 21-hour protocols for intravenous administration of ACC in case of paracetamol poisoning are equally effective in preventing liver damage, as evidenced by the results of the study: in both groups, when the antidote was started early (in the first 8 hours), there was no increase in ALT levels. The use of the 12-hour protocol for intravenous administration of ACC leads to a reduction in the duration of stay in the ICU by 1.5 times (p = 0.001), the duration of hospital treatment by 1.3 times (p = 0.052) compared to the 21-hour protocol. The frequency of allergic reactions during the 21-hour protocol of ACC administration was 10%; with the 12-hour ACC scheme, no allergic reactions were noted.Conclusions. The data obtained show that both protocols for the administration of ACC, when used early, are equally effective in preventing toxic liver damage, while the administration of ACC according to the 12-hour protocol leads to fewer adverse reactions, a reduction in the duration of stay in the ICU and the duration of hospitalization.