BackgroundWhile cancer is a risk factor for developing thromboembolism, so is the use of molecularly targeted therapies. This study aimed to determine whether thromboembolism incidence differed between vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitor use in patients with unresectable advanced or recurrent colorectal cancer, and to compare the risk of thromboembolism caused by cancer and the use of molecular targeted therapy drugs.Main bodyWe retrospectively evaluated patients with unresectable advanced or recurrent colorectal cancer who were treated with a cytotoxic anticancer drug and a VEGF or EGFR inhibitor combination between April 2016 and October 2021. Patients were compared in terms of the regimen administered, thromboembolism occurrence during the first-line treatment period, patient background, and clinical laboratory values. Of the 179 included patients, 12 of 134 (8.9%) in the VEGF-inhibitor group and 8 of 45 (17.8%) in the EGFR-inhibitor group developed thromboembolism, with no significant difference between the groups (P= 0.11). There was no significant difference in time to thromboembolism between patients in the VEGF- inhibitor group and patients in the EGFR-inhibitor group (P= 0.206). The cutoff value determined by a receiver operating characteristic analysis for the occurrence of thromboembolism was one point. Multivariate analysis using the occurrence of thromboembolism as the response variable identified at least one risk factor for thromboembolism (odds ratio = 4.17,P= 0.006, 95% confidence interval = 1.51–11.50). Molecular targeted therapies were not identified as a risk factor.ConclusionsAlthough the small sample size, there was no difference in the incidence of thromboembolism between the two molecular-targeted therapies in first-line treatment of patients with unresectable advanced or recurrent colorectal cancer. Our results suggest that risk factors for thromboembolism may be more strongly influenced by cancer itself than by the use of molecularly targeted therapies.