Abstract: Objective: The aim of this study is to evaluate the diagnostic efficacy of quantitative computed tomography (CT) in differentiating between connective tissue disease-associated interstitial lung abnormalities (CTD-ILA) and connective tissue disease-associated interstitial lung disease (CTD-ILD), as well as to establish a screening protocol for connective tissue disease (CTD) patients based on quantitative CT. Methods: A total of 140 patients with CTD-ILD, 33 patients with CTD-ILA, and 109 healthy controls were enrolled. Quantitative indices were obtained using the 3D-Slicer software. Results: Significant differences in quantitative CT indices are observed among the groups (p < 0.05). ROC analysis shows that the F%, GGO%, SD, and kurtosis are sensitive indicators for differentiating the control group from those with CTD-ILA/ILD. Notably, the best SD is demonstrated in the early diagnosis of both the CTD-ILA (AUC = 0.862) and CTD-ILD (AUC = 0.923) groups. Further distinguishing between CTD-ILA and CTD-ILD shows the strong discriminatory ability of the SD (AUC = 0.649) and F% (AUC = 0.617). Multivariable stepwise logistic regression analysis shows that F%, GGO%, SD, and kurtosis are statistically significant in differentiating the control group from the CTD-ILA/ILD groups (p < 0.05). Conclusion: Quantitative CT is promising for the early diagnosis of CTD-ILA/ILD. Establishing a CTD screening protocol based on quantitative CT can facilitate precise patient management.