Quantum noise is common in CT images and is a persistent problem in accurate ventilation imaging using 4D-CT and deformable image registration (DIR). This study focuses on the effects of noise in 4D-CT on DIR and thereby derived ventilation data. A total of six sets of 4D-CT data with landmarks delineated in different phases, called point-validated pixel-based breathing thorax models (POPI), were used in this study. The DIR algorithms, including diffeomorphic morphons (DM), diffeomorphic demons (DD), optical flow and B-spline, were used to register the inspiration phase to the expiration phase. The DIR deformation matrices (DIRDM) were used to map the landmarks. Target registration errors (TRE) were calculated as the distance errors between the delineated and the mapped landmarks. Noise of Gaussian distribution with different standard deviations (SD), from 0 to 200 Hounsfield Units (HU) in amplitude, was added to the POPI models to simulate different levels of quantum noise. Ventilation data were calculated using the ΔV algorithm which calculates the volume change geometrically based on the DIRDM. The ventilation images with different added noise levels were compared using Dice similarity coefficient (DSC). The root mean square (RMS) values of the landmark TRE over the six POPI models for the four DIR algorithms were stable when the noise level was low (SD <150 HU) and increased with added noise when the level is higher. The most accurate DIR was DD with a mean RMS of 1.5 ± 0.5 mm with no added noise and 1.8 ± 0.5 mm with noise (SD = 200 HU). The DSC values between the ventilation images with and without added noise decreased with the noise level, even when the noise level was relatively low. The DIR algorithm most robust with respect to noise was DM, with mean DSC = 0.89 ± 0.01 and 0.66 ± 0.02 for the top 50% ventilation volumes, as compared between 0 added noise and SD = 30 and 200 HU, respectively. Although the landmark TRE were stable with low noise, the differences between ventilation images increased with noise level, even when the noise was low, indicating ventilation imaging from 4D-CT was sensitive to image noise. Therefore, high quality 4D-CT is essential for accurate ventilation images.