Objective To compare clinical outcomes of percutaneous nephrolithotomy (PCNL) in patients who initially presented with and without urosepsis. Methods The study included patients who underwent PCNL for renal and ureter urolithiasis removal from January 2010 to December 2014 in our hospital. A 1∶1 matched-pair analysis was performed to compare outcomes and complications of patients who had obstructive urolithiasis with urosepsis initially (OUU) with patients who had obstructive urolithiasis with no urosepsis initially (NOUU) before PCNL. Results A total of 172 patients were included involving 122 (71%) males and 50 (29%) females with a mean age of 46.2 years (range 32 to 65 years). There were no significant differences between two groups in age, gender, BMI, complications, the size of the stones, stone's number and stone location (P>0.05). OUU groups had the similar stone-free rates (86.0%vs. 84.8%, P=0.829) as the NOUU group. OUU group had higher overall complications rate, longer duration of nephrostomy tube (NT), longer hospital length of stay (LOS), longer courses of postoperative antibiotics and higher grade of antibiotics after PCNL (all P<0.05). Higher fever developed postoperatively (11.6%vs. 3.5%, P=0.043), higher asymptomatic bacteriuria (11.6% vs. 3.5%, P=0.043) and symptomatic urinary tract infections (10.5% vs. 2.3%, P=0.029) were also found in OUU groups. There was no significant difference between two groups in sepsis (2.3% vs. 1.2%, P=0.560). Conclusion PCNL after decompression for urolithiasis-related urosepsis has similar success but higher complication rates than obstructive urolithiasis with no urosepsis initially.