Objectives Respiratory motion during PET imaging introduces quantitative and diagnostic inaccuracies, which may result in non-optimal patient management. This study investigated the effects of respiratory gating on image quantification using an amplitude-based optimal respiratory gating (ORG) algorithm. Methods Whole body FDG-PET/CT was performed in 66 lung cancer patients. The respiratory signal was obtained using a pressure sensor integrated in an elastic belt placed around the patient’s thorax. ORG images were reconstructed with 50 %, 35 %, and 20 % of acquired PET data (duty cycle). Lesions were grouped into anatomical locations. Differences in lesion volume between ORG and non-gated images, and mean FDG-uptake (SUVmean) were calculated. Results Lesions in the middle and lower lobes demonstrated a significant SUVmean increase for all duty cycles and volume decrease for duty cycles of 35 % and 20 %. Significant increase in SUVmean and decrease in volume for lesions in the upper lobes were observed for a 20 % duty cycle. The SUVmean increase for central lesions was significant for all duty cycles, whereas a significant volume decrease was observed for a duty cycle of 20 %. Conclusions This study implies that ORG could influence clinical PET imaging with respect to response monitoring and radiotherapy planning.