Abstract Introduction/Objective Phosphodiesterase-5 inhibitors (PDE5i) are traditionally employed for the management of erectile dysfunction and lower urinary tract symptoms. However, their role in the healing of complex penile wounds remains scarcely discussed. This study aims to describe the case of a 27-year-old man who suffered from penile strangulation, treated with sildenafil. Additionally, a literature review concerning the use of PDE5i for the treatment of complex penile injuries will be conducted. Methods A 27-year-old man presented to the emergency room after a self-induced penile strangulation using a ring placed at the base of the penis. Extensive necrosis of the corpus cavernosum was identified through magnetic resonance imaging. Considering the psychosocial implications of penile amputation, organ preservation was chosen, and conservative treatment with sildenafil and daily local dressings was initiated. Thirty days after admission, Doppler ultrasound revealed symmetrical corpus cavernosum with normal echogenicity and usual blood flow patterns. Subsequently, the patient underwent superficial necrotic tissue debridement followed by partial skin grafting in a second stage, leading to hospital discharge after 55 days of hospitalization. Results PDE5 inhibitors enhance nitric oxide bioavailability, promoting vasodilation and improved tissue oxygenation, thereby facilitating various phases of the healing process. Evidence indicates their benefit in microvascular perfusion in skin and soft tissues. Reports suggest satisfactory outcomes of topical PDE5i application in radiation-induced lesions, implying their role in epidermal cell expansion, reduction of inflammatory infiltrates, enhanced vascularization, and decreased collagen deposition. Conclusion This study presents a successful case of sildenafil use in treatment of a complex penile wound, shedding light on an unconventional application of PDE5i. Financing No conflict.