Abstract Background The acceptance of coronary CT angiogram (CCTA) scans in the management of stable angina has led to an exponential increase in studies performed and reported incidental findings, including pulmonary nodules (PN). Using low-dose CT scans, volumetry tools are used in growth assessment and risk stratification of PN between 5 and 8 mm in diameter. Volumetry of PN could also benefit from the increased temporal resolution of CCTA scans, potentially expediting clinical decisions when an incidental PN is first detected on a CCTA scan, and allow for better resource management and planning in a Radiology department. This study aims to investigate how cardiopulmonary hemodynamic factors impact the volumetry of PN using CCTA scans. These factors include the cardiac phase, vascular distance from the main pulmonary artery (MPA) to the nodule, difference of the MPA diameter between systole and diastole, nodule location, and cardiomegaly presence. Materials and methods Two readers reviewed all CCTA scans performed from 2016 to 2019 in a tertiary hospital and detected PN measuring between 5 and 8 mm in diameter. Each observer measured each nodule using two different software packages and in systole and diastole. A multiple linear regression model was applied, and inter-observer and inter-software agreement were assessed using intraclass correlation. Results A total of 195 nodules from 107 patients were included in this retrospective, cross-sectional and observational study. The regression model identified the vascular distance (p < 0.001), the difference of the MPA diameter between systole and diastole (p < 0.001), and the location within the lower or posterior thirds of the field of view (p < 0.001 each) as affecting the volume measurement. The cardiac phase was not significant in the model. There was a very high inter-observer agreement but no reasonable inter-software agreement between measurements. Conclusions PN volumetry using CCTA scans seems to be sensitive to cardiopulmonary hemodynamic changes independently of the cardiac phase. These might also be relevant to non-gated scans, such as during PN follow-up. The cardiopulmonary hemodynamic changes are a new limiting factor to PN volumetry. In addition, when a patient experiences an acute or deteriorating cardiopulmonary disease during PN follow-up, these hemodynamic changes could affect the PN growth estimation.