To test whether texture analysis (TA) can discriminate between Systemic Sclerosis (SSc) and non-SSc patients in computed tomography (CT) with different radiation doses and reconstruction algorithms.In this IRB-approved retrospective study, 85 CT scans at different radiation doses [49 standard dose CT (SDCT) with a volume CT dose index (CTDIvol) of 4.86 ± 2.1 mGy and 36 low-dose (LDCT) with a CTDIvol of 2.5 ± 1.5 mGy] were selected; 61 patients had Ssc ("cases"), and 24 patients had no SSc ("controls"). CT scans were reconstructed with filtered-back projection (FBP) and with sinogram-affirmed iterative reconstruction (SAFIRE) algorithms. 304 TA features were extracted from each manually drawn region-of-interest at 6 pre-defined levels: at the midpoint between lung apices and tracheal carina, at the level of the tracheal carina, and 4 between the carina and pleural recesses. Each TA feature was averaged between these 6 pre-defined levels and was used as input in the machine learning algorithm artificial neural network (ANN) with backpropagation (MultilayerPerceptron) for differentiating between SSc and non-SSc patients.Results were compared regarding correctly/incorrectly classified instances and ROC-AUCs.ANN correctly classified individuals in 93.8% (AUC = 0.981) of FBP-LDCT, in 78.5% (AUC = 0.859) of FBP-SDCT, in 91.1% (AUC = 0.922) of SAFIRE3-LDCT and 75.7% (AUC = 0.815) of SAFIRE3-SDCT, in 88.1% (AUC = 0.929) of SAFIRE5-LDCT and 74% (AUC = 0.815) of SAFIRE5-SDCT.Quantitative TA-based discrimination of CT of SSc patients is possible showing highest discriminatory power in FBP-LDCT images.