Abstract Background The factors affecting intra-operator variability of two-dimensional shear wave elastography (2D-SWE) have not been clearly established. We evaluated 2D-SWE variability according to the number of measurements, clinical and laboratory features, and liver stiffness measurements (LSM). Methods At least three LSM were performed in 452 patients who underwent LSM by 2D-SWE (supersonic shear imaging) out of an initial database of 1650 patients. The mean value of the three LSM was our best measurement method. Bland–Altman plots were used to evaluate intra-operator variability when considering only one, or the first two measurements. Variability was assessed by taking the absolute value of the difference between the first LSM and the mean of the three LSM. Logistic regression was used to assess the factors associated with the highest tertile of variability. Results The limit of agreement was narrower with the mean of the first and second measurements than with each measurement taken separately (− 2.83 to 2.99 kPa vs. − 5.86 to 6.21 kPa and − 5.77 to 5.73 kPa for the first and second measurement, respectively). A BMI ≥ 25 kg/m² and a first LSM by 2D-SWE ≥ 7.1 kPa increased the odds of higher variability by 3.4 and 3.9, respectively. Adding a second LSM didn’t change the variability in patients with BMI < 25 and a first LSM by 2D-SWE < 7.1 kPa. Conclusions Intra-operator variability of LSM by 2D-SWE increases with both a high BMI and high LSM value. In patients with BMI < 25 kg/m² and a first LSM < 7.1 kPa we recommend performing only one LSM.