Background and aim: The aim of this study is to evaluate whether the long-term (>_4 weeks) use of proton pump inhibitors (PPIs) is a risk factor for intubation requirement and mortality in patients hospitalized for COVID-19. Materials and methods: In this multicentric retrospective study, a total of 382 adult patients (>_18 years of age) with confirmed COVID-19 who were hospitalized for treatment were enrolled. The patients were divided into two groups according to the periods during which they used PPIs: the first group included patients who were not on PPI treatment, and the second group included those who have used PPIs for more than 4 weeks. Results: The study participants were grouped according to their PPI usage history over the last 6 months. In total, 291 patients did not use any type of PPI over the last 6 months, and 91 patients used PPIs for more than 4 weeks. Older age (HR: 1.047, 95% CI: 1.026-1.068), current smoking (HR: 2.590, 95% CI: 1.334-5.025), and PPI therapy for more than 4 weeks (HR: 1.83, 95% CI: 1.06-2.41) were found to be independent risk factors for mortality. Conclusion: The results obtained in this study show that using PPIs for more than 4 weeks is associated with negative outcomes for patients with COVID-19. Patients receiving PPI therapy should be evaluated more carefully if they are hospitalized for COVID-19 treatment.