Background: Medical treatment accomplished good results in the treatment of erectile dysfunction (ED). However, these results were temporary, whereby approximately 80% of the patients experienced drop out. Penile prosthesis insertion is an outstanding treatment for patients with ED who are refectory to medical treatment or those who desired to leave off pharmacotherapy to gain lasting treatment. Objectives: To assess the safety, efficacy, and sexual and psychological satisfaction among patients with ED who were subjected to subcoronal or infrapubic penile prosthesis implantation. Patients and Methods: The present study was a prospective case-control study that was carried out at Al-Azhar University Hospitals through the entire period of 2016 to 2020. Men with ED that did not respond to medical treatment and had vasculogenic impotence based on penile duplex were included in the study. All patients were submitted to clinical evaluation comprised of detailed sexual and urological history, and physical evaluation. All patients were subjected to frequent follow-up assessment visits for six months after the surgery. Results: This study included a total of 18 patients with ED. Out of them, 9 (50%) patients were subjected to the infrapubic approach, while 9 (50%) patients were treated with the subcoronal approach. Three months postoperatively, all men revealed an average penile length at maximum inflation of 13.4 cm (9.3-17.5 cm). This status was continued for six months in which no patient lost his penile length. Among patients treated with the subcoronal approach, one patient developed penile extrusion one and half months post-operatively due to wound dehiscence secondary to uncontrolled DM. As for the infrapubic group, a patient developed superficial infection and wound dehiscence and responded to antibiotic use and secondary suturing. Another case developed a hypertrophic scar. Conclusion: Erectile dysfunction can be safely and effectively treated by implantation of the penile prosthesis by the subcoronal approach. This approach achieved high satisfactory functional, aesthetic, and psychological outcomes relative to the infrapubic approach.