Memsorb™ (DMF Medical, Halifax, Canada) is a novel device based upon membrane oxygenator technology designed to eliminate CO2 fromexhaled gas when using a circle anesthesia circuit. Exhaled gases pass through semipermeable hollow fibers and sweep gasflowing through these fibers creates a diffusion gradient for CO2 removal. In vivo Memsorb™ performance was tested during target-controlled closed-circuit anesthesia (TCCCA) with desflurane in O2/air using a Zeus IE® anesthesia workstation(Dräger, Lübeck, Germany). Clinical care protocols for using this novel device were guided by in vitro performance results from a prior study (submitted simultaneously). After IRB approval, written informed consent was obtained from 10 ASA PS I-III patients undergoing robot-assisted radical prostatectomy. TCCCA targets were 39% inspired O2 concentration (FIO2) and 5.0% end-expired desflurane concentration (FETdes). Minute ventilation (MV) was adjusted to maintain 4.5-6.0% FETCO2. The O2/air (40% O2) sweep flow into the Memsorb™ was manually adjusted in an attempt to keep inspired CO2 concentration (FICO2) ≤ 0.8%. The following data were collected: FIO2, FETdes, FICO2, FETCO2, MV, fresh gas flow (FGF, O2 and air), sweep flow, and cumulative desflurane usage (Vdes). Vdes of the Zeus IE®-Memsorb™ combination was compared with historical Vdes observed in a previous study when soda lime (DrägerSorb 800 +) was used. Results are reported as median and inter-quartiles. A combination of manually adjusting sweep flow (26 [21,27] L/min) and MV sufficed to maintain FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, except in one patient in whom the target Zeus IE® FGF had to be increased to 0.7 L/min for 6min. FIO2 and FETdes were maintained close to their targets. Zeus IE® FGF after 5min was 0 [0,0] mL/min. Average Vdes after 50min was higher with Memsorb™ (20.3mL) compared to historical soda lime canister data (12.3mL). During target-controlled closed-circuit anesthesia in patients undergoing robot-assisted radical prostatectomy, the Memsorb™ maintained FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, and FIO2 remained close to target. Modest amounts of desflurane were lost with the use of the Memsorb™. The need for adjustments of sweep flow, minute ventilation, and occasionally Zeus IE® FGF indicates that the Memsorb™ system should preferentially be integrated into an automated closed-loop system.