Optimizing arrangement of prestressing tendons is a crucial aspect for calculation and design of frames with interior large-span neighboring two exterior small-spans. To maximize the capacity of critical section, prestressing tendons required in interior large-span are often arranged as continuous curve and extended as horizontal straight line to the side columns in two neighboring small-spans. This arrangement generates only upward prestress equivalent load in interior large-span, which could balance the vertical load in interior large-span effectively. While both of interior large-span and two neighboring exterior small-spans were concerned together as a single flexural member, and prestressing tendons were arranged as continuous curves, thus the equivalent load due to tensioning tendons would effectively balance the vertical loads both in interior large-span and two exterior small-spans. This arrangement can optimally realize the concept of load balancing. For a typical project, the differences in distribution and amplitudes of combination moment, major moment and second moment between two types of prestressing tendon profiles under the same conditions were analyzed. The influences on flexural capacity of normal section of two profiles were compared, and the rationality of continuous multi-curvature parabola profile in frames with interior large-span and neighboring exterior small-spans was validated.