OBJECTIVES: To investigate the optimal imaging protocols for enhanced chest CT to achieve good image quality and diagnostic performance with a lower radiation dose. MATERIALS AND METHODS: This IRB-approved study included both phantoms and patients. Two phantoms were scanned using 4 scanning modes. Images in each group were reconstructed using adaptive statistical iterative reconstruction-V (ASiR-V) at three strength levels of 40%, 60%, and 80%, denoted A1-3-D1-3, respectively with 1-3 representing the three ASiR-V levels. The image quality and radiation dose were evaluated to obtain the best imaging mode. 48 patients underwent contrast-enhanced standard dose CT (SDCT, protocol A) and low-dose CT (LDCT, protocol D) of the chest for follow-up. The image quality, radiation dose, and volume measurements of the left lung, right lung, and trachea using an AI-based software were compared. RESULTS: In the phantom study, D2 protocol which had the lowest dose, was selected as the optimal imaging protocol for enhanced chest CT. Compared with SDCT, LDCT reduced the radiation dose by 45% compared to SDCT. Images in LDCT with ASiR-V60% had similar noise as the standard SDCT images with the standard ASiR-V40%, but they had higher SNRs and CNRs. In addition, the volumes of the left lung, right lung, and bronchus did not significantly differ between the two groups. CONCLUSION: The combination of Auto-kV prescription and ODM