Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal illness with symptoms of heartburn, chest pain, and regurgitation. Management of GERD could involve proton pump inhibitor (PPI) medications, lifestyle modifications (healthy diet and diaphragmatic breathing exercises), and surgical intervention depending on the patients` condition. Aim:  To evaluate the impact of different management approaches on clinical symptoms among patients with gastroesophageal reflux disease. Research design: Nonequivalent quasi experimental research design was utilized in this study. Study Setting: This study was conducted in gastrointestinal unit at kafrelsheikh University Hospital. Study sample: A convenient sample of 90 patients with gastroesophageal reflux disease were divided randomly into 3 groups receiving Proton pump inhibitor (maximum dose), Proton pump inhibitor (medium dose) with lifestyle modifications, and lifestyle modifications only. Tools: Two tools for data collection were used in this study as follow: tool (I) structured interview questionnaire and tool (II) GERD questionnaire which used to assess patients GERD levels in pre, post intervention and follow up stages. Results: the results showed significant decrease in GERD levels among patients receiving PPI, patients receiving PPI with lifestyle modifications, & patients receiving lifestyle modifications only as (X2=24.471&p= 0.001, X2=27.432&p= 0.001 & X2=5.085&p= 0.278) consequently. In addition, repeated measures one way ANOVA test showed a statistical difference between the total GERD mean scores in relation to time of intervention among patients receiving PPI combined with lifestyle modifications followed by PPI group as (F=17.131&p=<0.05) & (F=4.768 &p=<0.05) accordingly. Conclusion:  Combination of pharmacological agent as Omeprazole (PPI) 20 mg/day with non-pharmacological nursing interventions as life style modifications in the form of dietary modifications and diaphragmatic breathing consider as the most effective method to reduce GERD clinical symptoms among patients with GERD. Recommendations: nurses' role as an educator should be continue to teach patients with GERD about lifestyle modifications and its positive effect on reducing the clinical symptoms of the disease. Provide continuous education about the latest modalities in this filed for nurses working with patients with gastrointestinal problems.