Proton pump inhibitors (PPIs) are a class of drugs used as the first-line therapy to treat gastroesophageal reflux disease (GERD). PPIs are metabolized mainly by cytochrome P450 2C19 (CYP2C19). The aim of the pilot study was to map the use of these drugs in Czech patients with various degrees of GERD and to analyze their individual variability in the gene encoding the CYP2C19. A total of 280 subjects (mean age±standard deviation: 46.23±13.11 years) were enrolled in the study: 95 patients with non-erosive reflux disease (NERD), 124 with reflux esophagitis (RE) and 61 with Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC). The diagnosis was determined on the basis of clinical symptoms such as heartburn (pyrosis) and/or acid regurgitation; objectified with 24-h pH-metry, esophagogastroduodenoscopy and manometry. The determination of genotypes of two polymorphisms in the CYP2C19 gene (*17 rs12248560 and *2 rs4244285) was based on the principle of real-time polymerase chain reaction with TaqMan assays. Almost 90% patients with GERD took one or more PPIs (omeprazole, pantoprazole and/or lansoprazole). In addition, 37% patients took some prokinetics and 16.4% patients had polypragmasy. The results of haplogenotype analyses of the CYP2C19 gene classified 36.8% patients into a group of extensive metabolizers (*1*1/*1*1) or even ultrarapid metabolizers 37.2% (*1*1/*1*17 and *1*1/*17*17); only smaller numbers of patients were intermediate or poor metabolizers (17.1% or 1.4%, respectively). We concluded that the most common loss-of-function CYP2C19*2 and gain-of-function CYP2C19*17 variants should be examined in patients with GERD before PPI pharmacotherapy is prescribed. Selection of adequate drugs and their proper dosing may contribute to improve patients’s life quality and prevent the progression to more severe GERD conditions such as BE and EAC.