To perform a systematic review and meta-analysis for the evaluation of 22 drug interventions in the management of ureteral stones, MEDLINE, Web of Science, EMBASE, and Cochrane central databases were searched to identify RCTs focusing on the evaluation of the efficacy of multiple drug interventions in medical expulsive therapy (MET) for ureteral stones, with no restrictions on year or language. Study quality assessment and data extraction were performed by independent reviewers. Major outcome measures were the stone expulsion rate, stone expulsion time, and pain episodes during treatment. A total of 78 RCTs with 14,922 participants were included in the present study. The final comparative results show that naftopidil plus corticosteroids was associated with higher stone expulsion rates than other drug interventions. Silodosin plus tadalafil had the highest probability of reducing stone expulsion time. Tamsulosin plus tadalafil performed better than all the other drug interventions in reducing pain episodes during treatment. However, in terms of all the outcome measures, the ranking plot results demonstrate that silodosin plus tadalafil, in addition to tamsulosin plus tadalafil and corticosteroids, was the best drug intervention as medical expulsive therapy in the management of ureteral stones. In ureteral stones <= 10 mm, all active drug interventions were more efficacious than the control; however, not all active drug interventions had an efficacy superior to the placebo. Silodosin plus tadalafil, tamsulosin plus tadalafil and corticosteroids, tamsulosin plus tadalafil, and naftopidil plus corticosteroids were the most effective drug interventions. Considering the choice of treatment, these results should serve as evidence-based practice and be considered by physicians, patients, and guideline developers. However, with respect to the limitations of the present study, further high-quality studies are needed for more in-depth evaluation of both the efficacy and safety of these drug interventions.