A precast, prestressed concrete girder with circular web openings allows building service systems (mechanical, electrical, communications, and plumbing) to cross the girder line within the member’s depth, reducing a building’s floor-to-floor height and the overall height of the structure. These height reductions have the potential to improve the competitiveness of total precast concrete structures versus other types of building systems. The experimental program reported in this paper tested five full-scale inverted-tee girders with circular web openings to failure, to evaluate the openings’ effect on girder behavior. The girders failed in a ductile manner due to diagonal cracking above the openings. The tested girders were designed using available recommendations in the existing literatures. It was observed that concrete fractured from tension zones around an opening, with cracks developing vetically towards the beam flanges. A beam would collapse when the cracks reached the flanges. In the present work, an analytical solution is developed for the load-deflection calculation of prestressed beam with web openings at any load stage. The solution assumes a trilinear deflection response characterized by the flexural cracking initiation, steel yielding, and ultimate capacity. Closed form expressions are presented for the case of simple beams subjected to four-points loading. These expressions are modified from present ACI code equations by incorporating appropriate laboratory determined coefficients in order to predict more precisely with some degree of conservativeness on flexural load-point deflection with any extent of uncracked, postcracked, and postyielded region along their spans. Accordingly, a simplified analysis procedure is developed by adopting a trilinear load-deflection response. The effectiveness of the simplified procedure is demonstrated by comparing its results to those of the analytical solution and the experimental values.