Urban highway construction megaprojects are commonly beset by significant and dynamic safety risks because of their large size, the scattered nature of the works involved, compressed construction schedules, technical difficulties and numerous participants. However, traditional on-site safety inspection cannot fully address all challenges, particularly those with behavior-based safety (BBS) risks. To deal with these challenges, this study describes the novel use of the proactive construction management system (PCMS) with a third-party safety inspection program. The definition, abstraction and implementation processes of the PCMS-aided third-party inspection program are demonstrated and tested through a case study of the Shanghai Central Loop Pudong highway construction project with multi-section sites. Based on a “before and after” comparative study, quantitative and qualitative data are triangulated to evaluate variations in the effectiveness of third-party inspection programs with and without the PCMS aided at the macro, meso, and micro levels. Results indicate the usefulness of the novel idea that applies the PCMS as a part of a third-party inspection program to improve BBS risk control on certain risky sites and incorporates its feedback into third-party inspection on all section sites to strengthen the overall safety training, safety inspection, and timely safety risk responses. These results not only provide an increased understanding of the role of PCMS in the safety management of highway megaprojects and the guidelines required for its future application but also serve as a precursor to future research into megaproject safety management.