ObjectiveTo investigate the prognostic relevance of serum triglyceride (TG) levels in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis-associated interstitial lung disease (ILD). Methods A retrospective data collection was conducted on patients diagnosed with anti-MDA5 antibody-positive dermatomyositis-associated ILD at West China Hospital of Sichuan University between February 2017 and July 2021. The clinical data, laboratory tests, and imaging examinations were collected, and the patients were followed up. According to the survival and death status of patients, they were divided into survival group and death group. According to TG levels, the patients were divided into a TG high level group and a TG low level group. We employed Cox proportional hazard models to investigate the variables linked to the mortality of individuals afflicted with anti-MDA5 antibody-positive dermatomyositis-associated ILD. Results A total of 204 patients with anti-MDA5 antibody-positive dermatomyositis-associated ILD were included. Among them, whose age ranged from 30 to 81 years old, with an average of (49.5±11.8) years old, there were 69 males and 135 females, 53 deaths and 151 survivors, 57 cases of rapidly progressive pulmonary interstitial fibrosis (RPILD) and 47 cases of non-RPILD. The results of multivariate Cox regression analysis showed that TG≥1.65 mmol/L, combined with RPILD, combined with dyspnea, age, lactate dehydrogenase≥321 U/L, and albumin<30 g/L were independent factors affecting the long-term prognosis of patients (P<0.05). The Kaplan-Meier method analysis results showed that the survival rate of the TG high level group was lower than that of the TG low level group (P=0.032). Conclusions Elevated TG levels can serve as a clinical indicator of adverse prognosis in patients with dermatomyositis-associated ILD who exhibit positive anti-MDA5 antibody status. Additionally, age, comorbidity with RPILD, combined with dyspnea, lactate dehydrogenase≥321 U/L, and albumin<30 g/L are independent factors contributing to the increased mortality risk among individuals with dermatomyositis-associated ILD who test positive for anti-MDA5 antibody.