Studies have demonstrated the direct relation between elevation in cardiac necrosis markers and increased risk of cardiovascular complications after percutaneous coronary intervention (PCI) in chronic kidney disease (CKD) patients. In this study, we sought to evaluate the effect of omega-3 on creatine kinase-MB (CK-MB) and troponin-I in CKD patients undergoing elective PCI. Methods: Eighty CKD patients, candidate for elective PCI, were randomly assigned into two groups: Group A – receiving omega-3 (2.5 g, 12 h before PCI) plus standard treatment (n = 37) and Group B – control group, receiving only standard therapy (aspirin 325 mg and clopidogrel 600 mg loading dose and weight-adjusted intravenous heparin) (n = 43). Blood samples were collected before and 24 h after PCI for measuring CK-MB and troponin-I. The primary endpoint was considered to be postprocedural variations of CK-MB and troponin-I levels in both groups. The secondary endpoint was the percentage of pre-procedural myocardial infarction (PMI) occurrence, defined as the elevation of post-PCI troponin-I, between study groups. Findings: Both the baseline and 24-h CK-MB were significantly higher in omega-3 group. Although 24-h troponin-I increased less in omega-3-treated arm compared to the control group, no statistically significant variation was observed between the two groups. With regard to PMI occurrence, no significant difference was detected among study groups. Conclusion: Despite the beneficial but nonsignificant effects of omega-3 on decreasing post-PCI elevation of troponin-I and PMI occurrence, further investigations with bigger study population, higher doses of omega-3 and longer duration of treatment, and long-term follow-up of patients are required to better test the potential effects of omega-3 in improving clinical outcomes in CKD patients undergoing PCI.