INTRODUCTION: Oral submucous fibrosis (OSMF) is a progressive, potentially malignant disorder often associated with areca nut and tobacco consumption. Dysplasia, a key predictor of malignant transformation, is poorly understood in terms of its association with clinical and histopathological factors. This study aimed to identify the clinical and histopathological predictors of dysplasia in OSMF to enhance diagnostic accuracy and risk stratification. MATERIALS AND METHODS: This retrospective observational study was conducted in the Department of Oral Pathology. A total of 545 case records were screened, and 120 histopathologically confirmed OSMF cases that met the strict inclusion and exclusion criteria were analyzed. Clinical parameters such as mouth opening, clinical staging, lesion site, and history of tobacco, smoking, and alcohol use were documented. Histopathological variables including epithelial keratinization, dysplasia, and epithelial thickness were evaluated. Statistical analyses, including logistic regression and discriminant analysis, were performed to identify significant predictors. RESULTS: Dysplasia was observed in 48 (40%) participants. Alcohol consumption was the strongest predictor of dysplasia (p = 0.0001), followed by epithelial thinning (p = 0.001), and smoking (p = 0.012). Reduced mouth opening was also significantly associated with dysplasia (p = 0.001). Keratinization and burning sensation were common but demonstrated minimal contribution to dysplasia risk. Discriminant analysis revealed that alcohol frequency and epithelial thinning were the most influential factors in distinguishing OSMF cases with dysplasia from those without dysplasia. CONCLUSION: This study identifies alcohol consumption, epithelial thinning, and smoking as significant predictors of dysplasia in patients with OSMF. Routine histopathological evaluations and targeted interventions addressing modifiable risk factors, particularly alcohol consumption and smoking, are critical for mitigating the risks of malignant transformation.