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Background: The present study aimed to validate a recently proposed algorithm for assistance titration during proportional assist ventilation with load-adjustable gain factors, based on a noninvasive estimation of maximum inspiratory pressure (peak P mus ) and inspiratory effort (pressure-time product [PTP] peak P mus )., Methods: Retrospective analysis of the recordings obtained from 26 subjects ventilated on proportional assist ventilation with load-adjustable gain factors under different conditions, each considered as an experimental case. The estimated inspiratory output (peak P mus ) and effort (PTP-peak P mus ) were compared with the actual-determined by the measurement of transdiaphragmatic pressure- and the derived PTP. Validation of the algorithm was performed by assessing the accuracy of peak P mus in predicting the actual inspiratory muscle effort and indicating the appropriate level of assist., Results: In the 63 experimental cases analyzed, a limited agreement was observed between the estimated and the actual inspiratory muscle pressure (-11 to 10 cm H 2 O) and effort (-82 to 125 cm H 2 O × s/min). The sensitivity and specificity of peak P mus to predict the range of the actual inspiratory effort was 81.2% and 58.1%, respectively. In 49% of experimental cases, the level of assist indicated by the algorithm differed from that indicated by the transdiaphragmatic pressure and PTP., Conclusions: The proposed algorithm had limited accuracy in estimating inspiratory muscle effort and with indicating the appropriate level of assist., Competing Interests: Drs Amargiannitakis and Gialamas contributed equally to this work. Drs Kondili, Vaporidi, and Georgopoulos have received lecture fees (honoraria) from Covidien., (Copyright © 2020 by Daedalus Enterprises.)