Introduction: Systemic sclerosis (SSc) is characterized by autoimmunity, inflammation, vasculopathy and fibrosis. Renin-angiotensin system (RAS) is implicated in similar pathophysiological mechanisms. The central molecule of RAS is angiotensin converting enzyme (ACE) whose activity is regulated by the insertion (II), deletion (DD) or codominant (ID) polymorphism in introne 16 of the ACE gene. DD polymorphism carriers have twice the ACE activity of those with II polymorphism. Hypothesis: ACE DD polymorphism carriers have more severe multiorgan manifestations of SSc. Aim: Analysis of the association between ACE gene polymorphism and phenotypic features of SSc. Patients and methods: Analysis of the association between severity of SSc multiorgan manifestations and ACE gene polymorphism was performed in 135, 105 and 70 patients at the time of diagnosis, after 5 and 10 years of follow-up, respectively. Results: No statistically significant association between ACE gene polymorphism and the severity of multiorgan SSc manifestations was found. At a time point after 10 years of follow-up, statistically significant differences between the 3 genotypes were found in C4 complement levels (lowest values in II, highest in DD genotype) and left ventricular ejection fraction (LVEF; lowest values in ID, highest in DD genotype). During 10 years of follow-up, there was a statistically significant decrease in erythrocyte sedimentation rate (ESR) and forced expiratory volume during the first second (FEV1) in genotype ID and increase in total sum of Medsger severity index in genotypes II and ID. Conclusion: Hypothesis that ACE DD polymorphism carriers have more severe multiorgan SSc manifestations has been rejected. II and ID genotype could be biomarkers of disease progression.