Background: The risk of periprocedural myocardial injury (PMI) during percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) may be underestimated because systematic cardiac biomarkers measurement was not performed in published studies. Objective: To evaluate the incidence, correlations, and clinical implications of periprocedural myocardial injury (PMI) during percutaneous coronary intervention (PCI) of successful chronic total occlusion (CTO) antegrade versus retrograde approach. Patients and methods: Between February 2018 and November 2019, the study included 80 patients with successful PCI to chronic total occlusion 60 patients with antegrade approach and 20 patients with retrograde approach after exclusion of failed PCI, renal failure, heart failure with moderate and severe reduced ejection fraction: cardiac biomarkers (CKMB) were performed to all patients before PCI and 12 hours after, to assess the periprocedural myocardial injury. PMI was defined as creatine kinase-myocardial band increase ≥3× the upper limit of normal, major adverse cardiac events (MACE) during mid-term follow up were evaluated. Results: Retrograde approach was used in 25% of all procedures PMI occurred in 9 patients (11.25%). The incidence of PMI was higher in patients treated with retrograde approach than antegrade approach (25%, 6,7% respectively p=0.039), during a median follow up of 6 months compared with patients without PMI. Those with PMI had a higher incidence of major adverse cardiac events (p= <0.001). Conclusions: PMI post CTO PCI was associated with the presence of several clinical, angiographic, and procedural factors, and has an adverse effect on 6-months clinical outcomes. These findings could be valuable for improving the quality of care for patients with CTO. The antegrade approach was more safe and effective than retrograde approach.