OBJECTIVES:To compare the previously defined six different histogram-based quantitative lung assessment (QLA) methods on high-resolution CT (HRCT) in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS:The HRCT images of SSc patients with ILD were reviewed, and the visual ILD score (semiquantitative) and the severity of ILD (limited or extensive) were calculated. The QLA score of ILD was evaluated using the previously defined six different methods and parameters (different lung attenuation ranges, skewness, kurtosis, mean lung attenuation, and standard deviation [SD]). Pulmonary function tests (PFTs) were also performed on all patients. Relationships among variables were evaluated using Spearman's correlation coefficient (r). Diagnostic performance of quantitative methods for the ability to differentiate the limited from extensive ILD was calculated using ROC analysis. RESULTS:Fifty-five patients were included in the study. There was a significant correlation between all quantitative and semiquantitative measurement results (p < 0.0001). The QLA scores revealed a significant correlation with PFT results. The kurtosis value of the voxels between - 200 and - 1024 Hounsfield unit (HU) (Method-5) showed the best correlation with semiquantitative evaluation (r = - 0.740, p < 0.0001). The ROC analysis demonstrated the best performance of SD of the voxels between - 400 and - 950 HU (Method-6) for histogram analysis method and Method-3 (voxels between - 260 and - 600 HU were calculated as ILD) for CT density cutoff methods. CONCLUSIONS:All the QLA methods are applicable in assessing the ILD score in SSc patients and have potential importance to differentiate limited from extensive ILD. KEY POINTS:• Quantitative interstitial lung disease assessment helps clinicians to assess systemic sclerosis patients with interstitial lung disease. • Quantitative lung assessment methods are applicable in assessing the interstitial lung disease score in systemic sclerosis patients. • Quantitative lung assessment methods have potential importance in the management of patients.