Background: Dual antiplatelet treatment (DAPT) duration after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is still being debated. We aimed to predict and reduce post-discharge bleeding after percutaneous coronary intervention. Methods: A prospective cohort study was conducted in Cardiology Department, Zagazig University Hospital from March 2022 to February 2023 and included 337 patients with acute coronary syndrome who underwent successful percutaneous coronary intervention (PCI). All patients who were successfully treated with 1 or more drug-eluting stents (DES) and adequately loaded with acetylsalicylic acid and clopidogrel or ticagrelor were included in the study. Platelets reactivity on aspirin, clopidogrel and ticagrelor were assessed after adequate loading period to ensure full antiplatelets effect. Results: Periprocedural bleeding was significantly associated with increase BMI (OR = 1.312, p = 0.0496), and number of lesions (OR = 5.26, p = 0.035). Also, bleeding was significantly associated with streptokinase use before PCI (OR = 128.644, p <0.001) and Unfractionated heparin dose during PCI and (OR = 1.002, p = 0.002). Conclusion: We can make prediction and reduction of post-discharge bleeding after percutaneous coronary intervention by control the risk factors, the proper daily use of PPI medications with DAPT and caution of flexion and extension of hip joint at site of vascular access of PCI in first 24 hours after discharge from hospital.