This study aimed at determining the choice and administration duration of ideal antibiotic prophylaxis before percutaneous nephrolithotomy (PNL) operation, a treatment modality for nephrolithiasis. The study included 90 patients who had no internal problem, yet had a negative urine culture and underwent a PNL operation. We compared infection rates between ciprofloxacin and ceftriaxone groups and their subgroups. The results showed no statistical difference between ciprofloxacin and ceftriaxone groups in terms of systemic inflammatory response syndrome (SIRS) (CIPp = 0.306, CTXP = 0.334. As a result of this study no statistical difference was observed between ciprofloxacin and ceftriaxone in terms of SIRS. It seems, however, reasonable to choose ceftriaxone, considering antibiotic sensitivity of microorganisms and detection of three cases accepted as urosepsis in the ciprofloxacin group. As there is no difference between short, and long-term prophylactic use of these antibiotics, preference of short-term prophylaxis for patients with no risk of infection will be important to avoid inappropriate antibiotic usage.