Background: Use of intracoronary calcium channel blockers (CCBs) during percutaneous coronary intervention (PCI) has been shown to have favorable effects on coronary blood flow. We aimed to investigate the effects of CCBs administrated perorally on creatine kinase-MB (CK-MB) levels in patients undergoing elective PCI. Methods: A total of 570 patients who underwent PCI were evaluated for CK-MB elevation. Patients who were on CCB therapy when admitted to the hospital constituted the CCB group. No CCBs were given to the rest of the patients during the periprocedural period and these patients served as the control group. Blood samples for CK-MB were obtained before and at 6 h, 24 h, and 36 h after the procedure. Results: 217 patients were in the CCB group (mean age 60.2 ± 9.3 years, 162 males), and 353 were in the control group (mean age 60.0 ± 10.1 years, 262 males). CK-MB levels increased above the normal values in 41 patients (18.9%) of the CCBs group and in 97 patients (27.5%) of the control group (p = 0.02). Median CK-MB levels were significantly higher in the control group for all studied hours (for all p < 0.05). Conclusions: Prior oral CCB therapy may have favorable effects in preventing myocyte necrosis after elective PCI.