The aim of our study is to evaluate portal and hepatic hemodynamic changes after N-acetylcysteine infusion in patients with systemic sclerosis. In an open-label study 40 patients with systemic sclerosis (SSc) were treated with 15 mg/kg/hour intravenous N-acetylcysteine for 5 consecutive hours in a single day. Hepatic flow volume, congestion index, portal flow volume, resistance index and pulse rate index were measured in each subject before and after infusion. In all patients mean hepatic flow volume (HFV) and mean portal flow volume (PFV) values after the five-hour infusion with NAC increased not significantly. In 22 selected patients with active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS)<18 and mild-moderate score to vascular domain of disease severity scale (DSS), mean HFV increased significantly when compared with mean HFV of 18 SSc patients with late capillaroscopic pattern, mRTSS>18 and severe-end stage score to vascular domain of DSS. The results of our study demonstrate that NAC is able to increase HFV and total liver perfusion after a single infusion in SSc patients with low disease activity and severity scores.