A method and system for estimating tissue parameters of a computational model of organ function and their uncertainty due to model assumptions, data noise and optimization limitations is disclosed. As applied to a cardiac use-case, a patient-specific anatomical heart model is generated from medical image data of a patient. A patient-specific computational heart model is generated based on the patient-specific anatomical heart model. Patient-specific parameters and corresponding uncertainty values are estimated for at least a subset of parameters of the patient-specific computational heart model. A surrogate model is estimated for a forward model of cardiac function, and the surrogate model is applied within Bayesian inference to estimate the posterior probability density function of the parameter space of the forward model. Cardiac function for the patient is simulated using the patient-specific computational heart model. The estimated parameters, their uncertainty, and the computed cardiac function are displayed to the user.
