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Mechanical ventilators are essential to patients who become critically ill from acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We utilized cost-effective, on-demand 3D printing (3DP) technology to produce critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swines. As one of the first studies to demonstrate splitting one anesthesia gas machine between two swines, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for individualized patient therapy. Our studies underscore that while possible, ventilator multiplexing is a complicated synergy between machine settings, circuit modification, and patient monitoring. Consequently, ventilator multiplexing is reserved only as a last emergency resource, by trained clinicians and respiratory therapists with ventilator operative experience.