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Abstract Background Urinary leakage after removal of the nephrostomy tube post-percutaneous nephrolithotomy (PNL) is a common complication which could be secondary to ureteral stone fragments, blood clots, ureteral edema at the ureteropelvic or ureterovesical junction, or rupture calyx. Unfortunately, it could impact the patient’s hospital stay causing it to be lengthy, delaying time to return to work, and the negative psychological effect. The current study aimed at assessing the role and effectiveness of alpha blockers (tamsulosin) in minimizing the duration of urinary leakage post-percutaneous nephrolithotomy (PNL). Methods In this prospective randomized clinical study, 62 cases of PNL were included. Physical examination, laboratory investigations and radiological work up (KUB and plain computed tomography) were done. Cases were randomized into two equal groups: Group A (31 cases) received tamsulosin perioperatively; Group B (31 cases) did not receive tamsulosin. The two groups were followed postoperatively as regards duration of urinary leakage, urinary catheterization and hospital stay. Results Duration of urinary leakage was statistically significantly shorter in group A (10.61 ± 6.66 h) compared to group B (21.48 ± 12.41 h) (p-value ˂ 0.001). Similarly, duration of hospital stay was shorter in group A (2.52 ± 0.72 days) compared to group B (3.10 ± 0.98) (p-value 0.020). Conclusions In patients undergoing PNL for renal stones and receiving tamsulosin, the duration of urinary leakage, and eventually hospital stay was shorter compared to those not receiving tamsulosin.