Introduction:Although some recent studies have found that original and generic clopidogrel brands are acceptable and have the same pharmacokinetic and pharmacodynamic properties, there is insufficient evidence to compare the clinical effectiveness and safety of brand and generic clopidogrel. The current study aims to evaluate the clinical safety of brand and generic clopidogrel by comparing clinical outcomes in patients undergoing carotid endarterectomy (CEA).Method:This was a single centre, parallel-arm, phase III, open-label, and randomized group sequential trial. It was conducted to compare the clinical safety of a brand and three generic clopidogrel forms in patients who have undergone CEA. All enrolled subjects were treated perioperatively with dual antiplatelet (aspirin and clopidogrel). The involved participants were assigned randomly into four groups based on the type of clopidogrel. Safety parameters were measured, including haematoma, blood draining from drainage, mouth deviation, tongue deviation, and stroke. SPSS software was used to perform the data analysis.Results:The trial included 80 patients in total (20 patients per group). Thirty-one (38.8%) patients were male. The mean age of patients was 65.6 years (49–79). Eighteen (22.5%) patients had a history of previous coronary intervention, and seventeen (21.3%) had symptomatic carotid artery stenosis. Overall, Plavix or Piax combined with aspirin were linked to better clinical safety than the other two generic clopidogrel, as the amount of bleeding was nearly two times lower in patients treated with Plavix or Piax (270±92.39 and 271.5±80.60, respectively) compared to PlavigrelAwa or Plavineer (505.7±169.1 and 496.5±174.6, respectively) (P≤0.001).Conclusion:The findings of the current study showed diversity in clinical safety of different clopidogrel formulations that were provided perioperatively in CEA patients.