Robot-assisted laparoscopic radical prostatectomy (RALRP) is a minimally invasive procedure; however, some amount of surgical trauma that can trigger systemic inflammation remains. Moreover, pneumoperitoneum during RALRP induces ischemia-reperfusion injury (IRI). Propofol, an anesthetic, is known to have anti-inflammatory and antioxidant properties. In the present study, we compared the effects of propofol with those of desflurane on inflammation and IRI during RALRP via measurements of different biomarkers and evaluation of perioperative renal function. Fifty patients were randomized to receive either desflurane (n = 25) or propofol (n = 25) with remifentanil during RALRP. Serum levels of interleukin (IL)-6 (IL-6), tumor necrosis factor alpha, C-reactive protein, and nitric oxide were measured 10 min after anesthesia induction (T1), 100 min after carbon dioxide (CO2) insufflation (T2), and 10 min after CO2 deflation (T3). Perioperative urine outputs and the serum creatinine level at 24 h after surgery were also recorded. We found that IL-6 levels at T2 and T3 were higher than those at T1 in both groups, although the increases were significant attenuated only in the propofol group. The other parameters showed no differences among the three time points in both groups. The intraoperative urine output was significantly higher in the propofol group than in the desflurane group, while the creatinine level showed no significant changes in either group. Our findings suggest that propofol can not only attenuate the inflammatory response during and after pneumoperitoneum in patients undergoing RALRP but also prevent oliguria during pneumoperitoneum.