Objective: To detect residual platelet aggregation following the switch from generic (GC) to brand clopidogrel (BC) in male patients after ST-elevated myocardial infarction (STEMI). Methods: The study was designed as an open-label, prospective cohort trial. Thirty-three male STEMI patients were enrolled. All patients received dual antiplatelet therapy with aspirin (100 mg/daily) and one of six GC at a daily dose of 75 mg. After 2 weeks, all patients were switched to BC. Adrenaline- and adenosine diphosphate (ADP)-induced platelet aggregation was assessed twice: on day 14 (before the switch) and on day 21 (after 1 week of BC therapy). Results: Adrenaline-induced platelet aggregation did not differ among clopidogrel formulations. In contrast, residual 5 µM ADP-induced platelet aggregation after BC differs from GC by 14% (28.0 ± 2.5 vs. 23.9 ± 2.1%; p = 0.03). When 20 µM ADP was used as agonist, the difference was smaller (36.2 ± 2.9 vs. 34.6 ± 2.8%) but still significant (p = 0.04) favoring BC. Conclusions: After 2 weeks of therapy, switching from GC to BC was associated with a mild but significant reduction in ADP-induced platelet aggregation in male post-STEMI patients. The observed differences between GC and BC should be confirmed in a larger randomized study, but may represent a risk in underdeveloped countries, where GC therapy is mandatory for post-MI inpatients.