ObjectiveTo investigate the correlation between the anterior talofibular ligament (ATFL) injury and the pathological changes of the anterior tibiotalar fat pad (ATFP) based on MRI. Methods The clinical and imaging data of 217 patients with ankle sprain who met the selection criteria between January 2019 and March 2024 were retrospectively analyzed. There were 113 males and 104 females with an average age of 38.2 years ranging from 18 to 60 years. Patients were divided into mild group (n=106), moderate group (n=63), and severe group (n=48) according to the degree of ATFL injury. There was no significant difference in gender, side, and body mass index among the 3 groups (P>0.05). The age of the mild group was significantly older than that of the moderate and severe groups (P<0.05). The imaging parameters including the longest and shortest sagittal axis, the largest thickness, the longest and shortest transverse axis, the ATFP area, the area of ATFP high-signal region, and the anterior distal tibial angle (ADTA) were measured according to the MRI and X-ray films of patients. According to the morphology of ATFP, the patients were divided into type Ⅰ (n=128), type Ⅱ (n=73), and type Ⅲ (n=16) based on the severity of the lesions. The distribution of ATFP types, ATFP area, area of ATFP high-signal region, and the ratio of area of ATFP high-signal region to ATFP area at the same level were statistically analyzed and compared among different ATFL injury groups. Additionally, radiographic parameters were compared across different ATFP types. Spearman rank correlation analysis was used to assess the relationships between ATFP area, area of ATFP high-signal region, and the ratio of area of ATFP high-signal region to ATFP area at the same level with patient baseline data. Through analysis of the area under curve (AUC) of ROC, optimal variables were selected for quantification to predict ATFL injury. Results There were significant differences in ATFP types among different ATFL injury groups (P<0.05). The mild group had a higher proportion of type Ⅰ, the moderate group had a higher proportion of type Ⅱ, and the severe group had higher proportions of both typeⅡ and type Ⅲ. No significant difference was found in ATFP area among the different ATFL injury groups (P>0.05). However, the area of ATFP high-signal region and the ratio of area of ATFP high-signal region to ATFP area at the same level were significantly lower in the mild group compared to the moderate and severe groups (P<0.05). Except for the longest sagittal axis, maximum thickness, and longest transverse axis, which were significantly smaller in ATFP types Ⅱ and Ⅲ compared to type Ⅰ (P<0.05), there was no significant difference in the remaining radiographic parameters among the different ATFP types (P>0.05). Spearman rank correlation analysis revealed that ATFP area was negatively correlated with patient gender (P<0.05), while area of ATFP high-signal region and the ratio of area of ATFP high-signal region to ATFP area at the same level were negatively correlated with patient age (P<0.05). Through analysis of the AUC for the response variable ATFP injury, the combined diagnostic AUC for the reciprocal of the maximum thickness and the reciprocal of the area of ATFP high-signal region was 0.839 (asymptotic P<0.001). The corresponding cutoff value when the Youden index reached its maximum was 0.570 3. ConclusionAs the severity of ATFL injury increases, the ATFP undergoes gradual morphological and functional changes. Classification based on ATFP types can assist in assessing the level of ATFL injury, thereby aiding in the prevention of post-traumatic osteoarthritis.