Introduction: Proton pump inhibitors (PPIs) are most prescribed medication classes and have similar efficacy between generic and brand names. PPIs are used for treatment upper GIT disorders. The aim of the present study was to evaluate the effectiveness and safety of proton pump inhibitors (PPIs). Methods: A cross sectional study conducted randomly on pharmacies, patients and Doctors to collect a data regarding the effectiveness and safely use of PPI through predesigned questionnaire containing information about dosage, types, side effect, effectiveness and safety of PPIs. The collected data was analysis by using Chi-square for determine the significant differences at α < 0.05. Result: The result of present study revealed numbers of points in which the questionnaire were intended for pharmacies, patients and doctors knowledge, effectiveness and safety of PPIs. The data gathered from pharmacy shown PPI dispensed without prescription (P< 0.05) in dose of 20 mg of omeprazole and for treatment of gastritis, stomachache and on medication use (P< 0.05). No side effect or any problem, safe, and effective of PPIs was from patients seeking PPIs to the drug dispensers. Furthermore, questionnaire for patients whom seeking treatment shown some similarity to pharmacies answers, however lack the knowledge about side effect of PPIs, and PPIs withdraw among patients. PPIs was found to be used by patients due to the advices of friends (P< 0.05). The last part in this study was doctors involved in which some common similarity were also identified between doctors, patients and pharmacies responses. Although, Doctors responses were revealed that PPIs should be used by prescription in single dose of common types of PPIs (P< 0.05). Conclusion: Due to the short time use of PPIs have been reported. This study suggested that, even no side effect and highly effective of PPIs reported, the PPIs should be monitoring and use under prescription.