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ObjectivesThe widespread use of proton pump inhibitors (PPIs) raised concerns on the safety of long-term use of these drugs. Community pharmacists have great responsibility of educating patients on these drugs which requires having adequate knowledge. The aim of this study was to assess the practices and knowledge of community pharmacists regarding PPIs.DesignThis was a cross-sectional study conducted by filling in a questionnaire. The questionnaire was developed after a comprehensive literature review and assessed knowledge and practices.SettingsCommunity pharmacists with at least 1 year of experience working in a community pharmacy were enrolled in the study.ParticipantsCommunity pharmacists with at least 1 year of experience working in a community pharmacy were enrolled in the study.Primary outcome measuresThe knowledge, attitudes, and practices of community pharmacists towards PPIs dispensing.ResultsA total of 459 community pharmacists were approached for participation in the study, 451 (98.3%) community pharmacists agreed to be enrolled. The most dispensed PPIs in Jordan were lansoprazole and the most commonly treated medical condition with PPIs was gastric ulcer. PPIs were dispensed by the pharmacists very frequently and one-fourth of the participants did not review instructions with patients to ensure their proper use of PPIs. Participants had an average knowledge of 6.1±1.7 (the highest knowledge score is 12). More than one-third of participants (180, 39.9%) had inadequate knowledge (a score of less than 6). Being a PharmD graduate was the only significant factor that predicted adequate knowledge in the logistic regression model, with an adjusted OR of 5.671, p=0.002.ConclusionTo provide adequate pharmaceutical care services, community pharmacists must possess appropriate knowledge on different aspects of PPIs concerning administration, efficacy and long-term and short-term side effects.