Patients surviving with a stroke have an increased risk for recurrent stroke. Clopidogrel is widely used to prevent recurrent stroke. However, clopidogrel may cause gastrointestinal bleeding (GIB). Therefore, proton pump inhibitors (PPIs) is recommended to reduce the side effect of clopidogrel. Unfortunately, these both drugs are metabolized in the liver by the same enzyme i.e. cytochrome P4502C19 (CYP219) that may reduce the effect of clopidogrel. The aim of this study was to evaluate the influence of PPIs on the effect of clopidogrel in the prevention of recurrent stroke. It was a hospital-based case control study conducted in Bethesda Private Hospital, Yogyakarta involving 392 patients with recurrent stroke as cases and 784 patients with first-ever stroke as controls. The exposure of PPIs during clopidogrel therapy on both cases and controls groups were recorded from prescription records for at least six months before index date. The duration of PPIs exposure were categorized as current expoure (less than two months before the index date) and recent exposure (2-6 months before the index date). The result showed there was no influence of PPIs exposure on the effect of clopidogrel on the risk of recurrent ischemic stroke (OR: 1.00; 95% CI: 0.56-1.79). Moreover, the current use of PPIs and clopidogrel could decrease the risk of recurrent ischemic stroke (OR: 0.04; 95% CI: 0.01-0.41). In conclusion, there is no association between PPI exposure and the risk of recurrent stroke in patients receiving clopidogrel.