Objective The objective of our study was to compare the image quality and radiation dose of computed tomography pulmonary angiography (CTPA) in patients with different body mass indexes using 100-kVp combination of different noise indexes (NIs) and 120-kVp scan protocol with the adaptive statistical iterative reconstruction 2.0 algorithm (ASiR 2.0). Methods A total of 120 patients who had undergone a CTPA were divided into 4 groups (A, B, C, and D), with 30 patients in each group. Group A underwent 120-kVp CT scan protocol in combination with NI = 25, while groups B, C, and D underwent 100-kVp CT scan protocol in combination with NI = 30, 35, and 40, respectively. All images were restructured using ASiR 2.0. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of all images were calculated when the CTPA was completed. Each subjective image evaluation used a 5-point scoring method and was conducted by 2 independent radiologists. The CT dose index of volume and dose-length product were recorded, and the mean value was calculated. The dose-length product was converted to the effective dose. Results There were no significant differences in SNR, CNR, and subjective image quality among the groups A, B, C, and D. The effective dose of group D decreased by 48.33% and 27.27% relative to groups A and B, respectively (P < 0.01). Conclusions The 100-kVp CT scan protocol in combination with NI = 40 can more effectively reduce the radiation dose than can the 120-kVp CT scan protocol in combination with NI = 25 for a CTPA while still maintaining diagnostic image quality.