Background <p>Oral epithelial dysplasia is histopathologically characterised by morphological and cellular changes. It is the most important predictive risk factor for progression into invasive neoplasm. Architectural and cytopathological characteristics have been updated by the World Health Organization in 2022. In India, The prevalence rate of OED and OSCC was 5.71% and 9.85% respectively.</p> Aims and Objectives <p>The aim of the study is to analyse and correlate the clinicopathological risk factors associated with malignant transformation in patients diagnosed with oral epithelial dysplasia (OED). We have attempted to classify the OED based on age, sex, site and associated habits and malignant transformation rate.</p> Materials and Methods <p>In this study, clinical data of 165 cases diagnosed histopathologically as oral epithelial dysplasia (OED) were retrieved from the Dental Information Archival Software (DIAS), Saveetha Dental College and Hospital, a total of 1367 cases reported between 2015 and 2018. The patient’s age, gender, anatomical site of biopsy, habit history and histopathological diagnosis were tabulated. Out of the 165 diagnosed OED cases, 46 cases that met the inclusion criteria and had complete follow-up data for 36 months were included in the final analysis. Cases with incomplete clinical records, loss to follow-up, or concurrent malignancies at initial diagnosis were excluded. Data were analysed using SPSS software v23 (IBM, Armonk, NY, USA) with ANOVA and Independent t-test.</p> Results <p>A cohort of 46 cases with OED were followed up for 36 months. At the time of initial diagnosis, 36% (<i>n</i> = 17) of the cases had severe epithelial dysplasia, 34% (<i>n</i> = 16) of cases had moderate epithelial dysplasia, and 28% (<i>n</i> = 13) of cases had mild epithelial dysplasia. After 36 months of follow-up, 8 cases exhibited clinical features suggestive of malignant transformation—such as non-healing ulceration, induration, increased lesion size, erythematous changes, and altered surface texture. Based on these findings, they were advised to undergo a second biopsy for histopathological confirmation. Of the 8 cases that underwent a second biopsy, 3 cases (8%) showed histopathological evidence of malignant transformation to oral squamous cell carcinoma (OSCC), characterized by invasive epithelial islands breaching the basement membrane, cellular atypia, and keratin pearl formation. These included previously diagnosed Moderate OED (<i>n</i> = 1) and Severe OED (<i>n</i> = 2). In contrast, the remaining 5 cases (10%) continued to exhibit dysplastic changes without evidence of invasion—comprising Moderate OED (<i>n</i> = 1) and Severe OED (<i>n</i> = 4)—and were therefore not considered malignant transformations. The remaining (82%) did not show any clinical change. There was no evidence of regression of lesions in the second biopsy.</p> Conclusion <p>To conclude, we observed the highest risk of malignant transformation in OED to OSCC within the first three years after initial diagnosis. Male patients, patients with a combination of deleterious habits, and patients with histologically severe grades of OED had an increased risk of malignant transformation. Further multicentric studies with larger cancer registries and studies on prognostic immunohistochemical markers can help us in deciphering the pathogenesis of OED into OSCC.</p>