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Introduction The aim of this study was to evaluate longitudinal changes in nailfold videocapillaroscopy (NVC) findings in systemic sclerosis (SSc) patients treated with intravenous tocilizumab (TCZ), an anti-IL-6 receptor antibody, and to analyze the association of these changes with the dynamics of clinical parameters and angiogenic factors in the patients’ sera.Material and Methods NVC parameters (capillary density, capillary dimension, capillary morphology, and micro-hemorrhages) were assessed using a semiquantitative scoring system in SSc patients treated with monthly intravenous TCZ (n=13). To explore the correlation between NVC findings and angiogenic mediators, we quantified serum levels of 7 pivotal angiogenic factors before and 6 months after TCZ initiation using a multiplex immunoassay.Results Capillary density significantly increased at 6 months compared with baseline. This increase was positively and strongly correlated with improvements in pulmonary function test results. Among the angiogenic factors, serum levels of vascular endothelial growth factor (VEGF)-A, platelet endothelial cell adhesion molecule (PECAM)-1, and hepatocyte growth factor (HGF) were significantly intercorrelated and significantly decreased after 6 months of treatment. Of note, serum HGF levels showed the strongest correlation with capillary density and were also significantly correlated with modified Rodnan skin score and %FVC. Furthermore, serum VEGF-A levels showed a significant correlation with %FVC, and the decrease in VEGF-A levels was robustly associated with improvements in pulmonary function test results.Conclusions Our results collectively suggest that TCZ treatment ameliorates systemic vascular abnormalities by modulating the pathogenic network of aberrant angiogenic factors in SSc, which are critically involved in the pathophysiology of SSc-associated interstitial lung disease.