Recent attention has been drawn to a potential drug-drug interaction observed between clopidogrel and proton pump inhibitors (PPIs). However, this potential interaction may not be a class effect of PPIs. We investigated if pantoprazole, which has a different metabolism than omeprazole, diminishes the effectiveness of clopidogrel. Our study included 336 patients (mean age 64.6 years; 106 women) 48 hours after percutaneous coronary stent implantation with a loading dose of 600 mg clopidogrel hydrogensulfate and 500 mg aspirin, followed by 75 mg clopidogrel and 100 mg aspirin daily. Whereas 188 patients (59 women) were not given any PPI comedication, 122 patients received pantoprazole and 26 either omeprazole or esomeprazole. The platelet aggregation followed by impedance aggregometry (in Ohm) was induced by 5 mmol/L adenosine diphosphate. The percentage of clopidogrel low-response (CLR) was similar between the non-PPI group [2.75 Ohm (confidence interval, CI: 2.25-3.26); 21.9% CLR] and the pantoprazole group [2.33 Ohm (CI: 1.79-2.87); 16.4% CLR] but higher in patients treated with omeprazole/esomeprazole (3.00 Ohm (CI: 1.49-4.51); 30.8% CLR). Multivariate regression analysis reveals that the risk of CLR in the pantoprazole comedication group was not increased compared with the group without any PPI [odds ratio 0.59 (CI: 0.31-1.13) 0.11]. Our data suggest that pantoprazole does not diminish the antiplatelet effectiveness of clopidogrel early after coronary stenting. Therefore, the use of pantoprazole seems preferable in patients treated with clopidogrel when a concomitant medication with a PPI is indicated.