Imaging of gastric cancer thickness is closely associated with the depth of tumor invasion, which provides guidance for clinical staging and assists the evaluation of the effects of adjuvant therapy. However, it is unclear whether the measurement of thickness is affected by the degree of gastric filling, and its accuracy and reliability are under-reported. The present study aimed to investigate the influence of the degree of gastric filling on the measurement of gastric cancer thickness. A total of 38 patients with advanced gastric cancer who underwent enhanced abdominal computed tomography (CT) scanning at the Department of CT and MR in The Fourth Hospital of Hebei Medical University (Shijiazhuang, China) between July and September 2016 were recruited, consisting of 21 newly diagnosed cases and 17 follow-up cases following non-surgical treatments. Plain scanning (prior to filling) and enhanced scanning in venous phase (following filling) were performed. Axial CT images prior to and following filling of the normal part of gastric wall and the lesions were compared. The same procedure was repeated on these participants 1 month later by the same radiologist, and the results were compared with those obtained previously. Normal gastric wall thickness prior to and following gastric filling was significantly different (all P<0.001) with the most substantial changes observed at the greater curvature. Lesion thickness prior to and following filling was similar in newly diagnosed patients, but significantly different in patients for re-examination (P<0.05). The two thickness measurements in the same patients were consistent. The measured thickness of gastric cancer in newly diagnosed patients was relatively stable, and could be used as an indicator in baseline CT examination. Maintaining a similar degree of gastric filling during re-examination could aid the accurate evaluation of treatment efficacy.