Objective: To compare valveless insufflation (AirSeal®) with a conventional insufflation system (CIS) during robotic prostatectomy (RP) and the ability to use ultralow pneumoperitoneum at 6 mm Hg with each system as well as comparison of physiologic outcomes and pain scores. Patients and Methods: We conducted a prospective study of 100 patients randomized to AirSeal or CIS during RP. The frequency of need for increasing pneumoperitoneum was assessed as well as arterial blood gases, respiratory/hemodynamic parameters, pain scores, and analgesic requirements. Quality of smoke evacuation and scope cleaning frequency were also measured. Results: All procedures were completed at 6 mm Hg without needing to increase pressures with either insufflator. There were no statistically significant differences in partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), HCO3, pH, carbon dioxide (CO2) elimination, or end-tidal carbon dioxide pressure (EtCO2) between groups. The AirSeal group had a lower maximum peritoneal pressure (7.9 vs 9.9 mm Hg, p < 0.001) but without differences in pain scores or analgesics. Surgeon-assessed smoke evacuation was poorer using CIS with more laparoscope cleanings in nonobese patients than with AirSeal (2.1 vs 3.0, p = 0.026). Conclusion: Valveless-trocar insufflation provided more stable pressure but without benefits in physiologic or pain parameters. Previously identified benefits may have been negated by being able to complete all procedures at ultralow pressure with either insufflator, although an expert bedside assistant moderating suction may have contributed to feasibility of maintaining low pressure with CIS. A randomized trial of 6 vs 15 mm Hg is currently underway. The ClinicalTrials.gov Identifier: NCT02114164.