Background Ureteroscopy had been recognized as a major method for treating ureteric calculi. Although invasive, the development of smaller and more flexible ureteroscopes, and a new generation of various intracorporial lithotripters, has made this procedure safer and more effective. Placing a ureteric stent after ureteroscopy with stone extraction is done by some urologists routinely to prevent possible stenosis or to decrease secondary pain caused by mucosal oedema. Objective To evaluate and compare the efficacy and safety of Tadalafil and Tamsulosin in reliving Double-J stent-related symptoms following uncomplicated ureteroscopic lithotripsy (URSL) and percutaneous nephrolithotomy (PCNL). Patients and Methods The present study was a prospective randomized comparative study conducted on 80 patients (56 men and 24 women) with double-J stent inserted following uncomplicated ureteroscopic lithotripsy (URSL) and unilateral percutaneous nephrolithotomy (PCNL) in Ain Shams University Hospital and Sohag Educational hospital over a period of 1 year. Results The study shows that Tadalafil is safe and effective in relieving DJ related symptoms. Tadalafil 5 mg once / day is as effective as Tamsulosin 0.4 mg once / day in relieving urinary symptom and body pain but more effective in relieving sexual symptoms and general health. Conclusion The study shows that Tadalafil is safe and effective in relieving DJ related symptoms. Tadalafil 5 mg once / day is as effective as Tamsulosin 0.4 mg once / day in relieving urinary symptom and body pain but more effective in relieving sexual symptoms and general health. Therefore Tadalafil 5 mg once / day could be recommended as preferred drug in sexually active patients undergoing DJ stenting.