Abstract Introduction Although visual and quantitative assessments of [18F]FDG PET/CT studies typically rely on liver uptake value as a reference or normalisation factor, consensus or consistency in measuring [18F]FDG uptake is lacking. Therefore, we evaluate the variation of several liver standardised uptake value (SUV) measurements in lymphoma [18F]FDG PET/CT studies using different uptake metrics. Methods PET/CT scans from 34 lymphoma patients were used to calculate SUVmax^liver, SUVpeak^liver and SUVmean^liver as a function of (1) volume-of-interest (VOI) size, (2) location, (3) imaging time point and (4) as a function of total metabolic tumour volume (MTV). The impact of reconstruction protocol on liver uptake is studied on 15 baseline lymphoma patient scans. The effect of noise on liver SUV was assessed using full and 25% count images of 15 lymphoma scans. Results Generally, SUVmax^liver and SUVpeak^liver were 38% and 16% higher compared to SUVmean^liver. SUVmax^liver and SUVpeak^liver increased up to 31% and 15% with VOI size while SUVmean^liver remained unchanged with the lowest variability for the largest VOI size. Liver uptake metrics were not affected by VOI location. Compared to baseline, liver uptake metrics were 15–18% and 9–18% higher at interim and EoT PET, respectively. SUV^liver decreased with larger total MTVs. SUVmax^liver and SUVpeak^liver were affected by reconstruction protocol up to 62%. SUVmax and SUVpeak moved 22% and 11% upward between full and 25% count images. Conclusion SUVmean^liver was most robust against VOI size, location, reconstruction protocol and image noise level, and is thus the most reproducible metric for liver uptake. The commonly recommended 3 cm diameter spherical VOI-based SUVmean^liver values were only slightly more variable than those seen with larger VOI sizes and are sufficient for SUVmean^liver measurements in future studies. Trial registration EudraCT: 2006–005,174-42, 01–08-2008.