Abstract Purpose To investigate the effects of mid-inspiratory respiration commands and other factors on transient interruption of contrast (TIC) incidence on CT pulmonary angiography. Methods In this retrospective study, 824 patients (mean age, 66.1 ± 15.3 years; 342 males) who had undergone CT pulmonary angiography between January 2021 and February 2023 were included. Among them, 545 and 279 patients were scanned at end- and mid-inspiratory levels, respectively. By placing a circular region of interest, CT attenuation of the main pulmonary artery (CT_MPA) was recorded. Associations between several factors, including patient age, body weight, sex, respiratory command vs. TIC and severe TIC incidence (defined as CT_MPA < 200 and 150 HU, respectively), were assessed using logistic regression analyses with stepwise regression selection based on Akaike’s information criterion. Results Mid-inspiratory respiration command, in addition to patient age and lighter body weight, had negative association with the incidence of TIC. Only patient age, lighter body weight, female sex, and larger cardiothoracic ratio were negatively associated with severe TIC incidence. Mid-inspiratory respiration commands helped reduce TIC incidence among patients aged < 65 years (p = 0.039) and those with body weight ≥ 75 kg (p = 0.005) who were at high TIC risk. Conclusion Changing the respiratory command from end- to mid-inspiratory levels, as well as patient age and body weight, was significantly associated with TIC incidence.