Abstract: Objective: To compare the quantitative parameters of lung HRCT and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive idiopathic inflammatory myopathy (IIM) patients with different prognoses. Methods: The clinical and imaging data of 19 MDA5 antibody-positive IIM patients admitted to Beijing Shijitan Hospital Affiliated with Capital Medical University between February 2017 and November 2022 were retrospectively analyzed. According to the prognoses, the patients were divided into the good prognoses group (14 cases) and the poor prognoses (intubation or death) group (5 cases). The clinical and laboratory indexes, types of interstitial lung disease (ILD), and CT quantitative indexes were compared between the two groups. Results: There were significant differences in gender; carcinoembryonic antigen; blood oxygen saturation; and the percentages of lymphocytes, monocytes, neutrophils, lymphocytes, and neutrophils between the good versus the poor prognoses groups. The proportion of abnormal respiratory system changes was higher in the poor prognoses group. In terms of the type of ILD, acute interstitial pneumonia (AIP)-like lesions were the main type in the poor prognoses group, and nonspecific interstitial pneumonia (AIP) lesions were the main type in the good prognoses group. For NSIP-like lesions, there was a statistically significant difference between the two groups. The semi-quantitative score of the poor prognoses group was higher, and the volume of whole lung lesions as well as the proportion of whole lung lesions were also higher. Spearman correlation analysis showed that the blood oxygen saturation, monocyte percentage, semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion were negatively correlated, while carcinoembryonic antigen, neutrophil percentage, and neutrophils were positively correlated with the semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion. Conclusions: The lung HRCT quantitative indicators, clinical manifestations, and laboratory indicators are different in MDA5 antibody-positive IIM patients with different prognoses. Early evaluation of HRCT imaging manifestations, clinical manifestations, and laboratory indicators is of great significance in determining the prognosis of MDA5 antibody-positive IIM patients, which provides corresponding support for clinical diagnosis and treatment.