Background: Pyonephrosis is a life-threatening infection of the obstructed renal collecting system requiring urgent drainage. Percutaneous nephrostomy (PCN) and double-J (DJ) stenting are the two primary decompression modalities, but comparative outcomes remain debated. Objective: To compare the efficacy, safety, time to infection resolution, and patient-reported discomfort between PCN and DJ stenting in pyonephrosis. Methods: A retrospective cohort of 200 adults with radiologically confirmed pyonephrosis managed between 2018–2024 was analyzed. Patients underwent either PCN (n=98) or DJ stenting (n=102). Primary outcome: time to clinical resolution. Secondary outcomes: complications, technical success, length of stay, and patient discomfort (VAS). Results: Clinical success was similar between PCN and DJ stenting (95.9% vs 94.1%, p=0.62). PCN demonstrated marginally faster infection resolution (2.8 ± 1.2 vs 3.3 ± 1.4 days; p=0.07). Pain scores favored DJ stenting (VAS 3.1 vs 5.6; p<0.001). Complication rates and length of hospital stay showed no significant differences. Conclusions: PCN and DJ stenting remain safe and effective drainage modalities. PCN provides a clinically relevant trend toward faster infection control, while DJ stenting results in higher patient comfort. Modality selection should be individualized.