ABSTRACT Objective To assess efficacy and safety of silodosin, tadalafil, versus combination of both medications as medical expulsive therapy (MET) for distal ureteric stones. Methods This prospective, double blinded, randomized clinical trial included 128 patients aged 18 years or more irrespective of gender who are presented to emergency department or outpatient with distal ureteric stones ranging in size from 5–10 mm, randomized into three groups: Group I (n = 42) received Silodosin 8 mg once daily, Group II (n = 44) received Tadalafil 5 mg once daily, and Group III (n = 42) received Silodosin 8 mg combined with Tadalafil 5 mg one daily. All participants underwent thorough history-taking, routine laboratory investigations, and clinical examinations. The primary end point included expulsion rate and time and treatment tolerance. Secondary end points were number pain episodes, need for emergency room visit, amount of analgesia, need for intervention. Results The expulsion rate was 71.4% for silodosin, 61.4% for tadalafil and 88.1% for combined therapy (p = 0.018). Expulsion time was significantly shorter after combined therapy 10.4 + 3.5 days, while after silodosin 14.1 + 4 days, while 17.8 + 3.4 days after tadalafil (p < 0.001). The number of pain episodes, emergency room visits, and the amount of analgesia were significantly in favour of combined therapy (p value 0.004, 0.010, and <0.001) respectively. Conclusions A combination of Silodosin with Tadalafil as a MET for distal ureteric stones is more effective than monotherapy with tolerable side effects.