This disclosure describes systems and methods for compensating for leakage when during delivery of gas to a patient from a medical ventilator in a pressure regulated volume control (PRVC) ventilation mode. The technology described herein includes systems and methods that compensate the delivery of PRVC ventilation for leakage in the patient circuit by using leak-compensated lung flows as well as respiratory mechanics (lung compliance and lung resistance) estimated in a manner that compensates for elastic and inelastic leaks from the ventilation system.