Objectives: The impact of antiepileptic drugs (AEDs) on atherosclerosis is not fully understood, but some studies have suggested that they may worsen the condition. Researchers have aimed to assess the effect of levetiracetam (LEV) on atherosclerosis progression in post-stroke patients by examining changes in carotid intima-media thickness (CIMT). This study sought to address the gap in the literature regarding the vascular safety of LEV and its role in managing epilepsy in individuals with a history of stroke, considering their increased cardiovascular risk. Materials and Methods: This cross-sectional study involved 120 post-stroke patients from a tertiary care center. Participants were divided into two groups: 60 receiving LEV and 60 not prescribed any anti-epileptic drugs (AEDs). The eligibility criteria included patients over 18 years of age with a history of ischemic or hemorrhagic stroke, non-diabetic status, and no significant systemic diseases affecting mobility or lipid profiles. CIMT was measured at baseline and one year using high-resolution B-mode ultrasonography. The study analyzed CIMT progression using the student’s t-test, Mann-Whitney U test, linear regression, ANCOVA, and repeated measures ANOVA to explore the impact of LEV on vascular health. Results: There were no significant differences in demographic or clinical profiles between the groups. Regression analyses indicated that age was a significant predictor of CIMT progression, with each additional year increasing CIMT by 0.02 mm (p = 0.046). Triglyceride levels also influenced CIMT, with each mg/dL increase contributing to a 0.001 mm rise (p = 0.048). Additionally, higher initial LDL levels significantly increased the CIMT by 0.003 mm for each unit increase (p = 0.003). ANCOVA revealed that LEV treatment did not significantly alter CIMT progression compared with non-users (F-value = 0.25, p = 0.617). Repeated Measures ANOVA showed stable CIMT progression over one year across all participants, with no significant differences between the groups or over time (main effect of time F-value = 0.59, p = 0.444; group effect F-value = 0.13, p = 0.720).  Conclusion: LEV does not significantly affect the progression of CIMT or disrupt lipid profiles in post-stroke patients, thereby not exacerbating atherosclerosis. These results affirm LEV's cardiovascular safety of LEV in a high-risk population, supporting its use in managing post-stroke epilepsy without added cardiovascular risk. This contributes to the growing evidence that newer-generation antiepileptic drugs, such as LEV, may offer a safer profile regarding vascular health than older medications.