Cervical shortening and cervical insufficiency contribute to a significant number of preterm births. However, the deformation mechanisms that control how the cervix changes its shape from long and closed to short and dilated are not clear. Investigation of the biomechanical problem is limited by (1) lack of thorough characterization of the three-dimensional anatomical changes associated with cervical deformation and (2) difficulty measuring cervical tissue properties in vivo. The objective of the present study was to explore the feasibility of using three-dimensional ultrasound and fundal pressure to obtain anatomically-accurate numerical models of large-strain cervical deformation during pregnancy and enable noninvasive assessment of cervical-tissue compliance. Healthy subjects (n = 6) and one subject with acute cervical insufficiency in the midtrimester were studied. Extended field-of-view ultrasound images were obtained of the entire uterus and cervix. These images aided construction of anatomically accurate numerical models. Cervical loading was achieved with fundal pressure, which was quantified with a vaginal pressure catheter. In one subject, the anatomical response to fundal pressure was matched by a model-based simulation of the deformation response, thereby deriving the corresponding cervical mechanical properties and showing the feasibility of noninvasive assessment of compliance. The results of this pilot study demonstrate the feasibility of a biomechanical modeling framework for estimating cervical mechanical properties in vivo. An improved understanding of cervical biomechanical function will clarify the pathophysiology of cervical shortening.