Objective: To investigate the value of synthetic magnetic resonance imaging (SyMRI) of the lacrimal gland in assessing disease activity of thyroid-associated ophthalmopathy (TAO). Methods: From January 2024 to January 2025, 73 patients diagnosed with TAO (29 in active phase, 58 eyes; 44 in inactive phase, 88 eyes) were prospectively enrolled in the First Affiliated Hospital of Nanjing Medical University. Quantitative parameters [T1 relaxation time (T1RT), T2 relaxation time (T2RT), proton density (PD)] and semi-quantitative parameters[signal intensity ratio (SIR) of the lacrimal gland to the temporal muscle on contrast-weighted images, including double inversion recovery (DIR) sequence, fluid-attenuated inversion recovery (FLAIR) sequence, and short tau inversion recovery (STIR) sequence] of the lacrimal glands were calculated based on SyMRI. The minimum, mean, and maximum values of these parameters were compared between groups. Multivariate logistic regression was employed to identify independent predictors of disease activity. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of individual imaging predictors and their combined model for TAO activity classification. Results: All quantitative and semi-quantitative parameters of the lacrimal gland (except for the minimum values of all parameters) were significantly higher in the active TAO group than those in the inactive TAO group(all P < 0.05). T1RTmean [adjusted odds ratio(AOR)=1.006, P=0.003], T2RTmean(AOR=1.127, P < 0.001), PDmax(AOR=1.071, P=0.001), and STIR-SIRmax(AOR=1.834, P=0.006) were identified as independent predictors of active TAO. The combined model integrating these four independent predictors achieved the highest diagnostic performance[area under the curve (AUC)=0.855], significantly outperforming T1RTmean (AUC=0.663), T2RTmean (AUC=0.725), PDmax (AUC=0.707), and STIR-SIRmax (AUC=0.755) when used individually(all P < 0.05). Conclusion: Quantitative and semi-quantitative SyMRI-derived parameters of the lacrimal gland may serve as objective and noninvasive imaging biomarkers for identifying active TAO and provide complementary information for disease activity assessment, particularly in patients with equivocal clinical activity score or limited ability to undergo clinical evaluation.