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We aimed to investigate the association between the preoperative platelet-to-lymphocyte ratio (PLR) and venous thromboembolism (VTE) in patients with head and neck cancer (HNC) undergoing major surgery.Retrospective cohort study.Academic tertiary hospital from 2011 to 2017.Patients with confirmed HNC undergoing major surgery were included in this study. The preoperative PLR was recorded for all patients. Known VTE risk factors, including Caprini score, age, sex, smoking, body mass index, prior VTE, and anticoagulation, were also recorded. Risk factors were screened in univariate analysis using Wilcoxon’s rank sum test and χ2 test (Bonferroni corrected). Significant covariates were included in a multivariate regression model. Bootstrap techniques were used to obtain credible confidence intervals (CIs).There were 306 patients enrolled with 7 cases of VTE (6 deep vein thromboses and 1 pulmonary embolism. On univariate analysis, length of stay (P = .0026), length of surgery (P = .0029), and PLR (P = .0002) were found to have significant associations with VTE. A receiver operator characteristic (ROC) curve was constructed that yielded an area under the ROC of 0.905 (95% CI, 0.82-0.98). Using an optimized cutoff, the multivariate model showed that length of surgery (β 95% CI, 0.0001-0.0006; P = .0056) and PLR (β 95% CI, 5.3256-5.3868; P < .0001) were significant independent predictors of VTE.This exploratory pilot study has shown that PLR offers a potentially accurate risk stratification measure as an adjunct to current tools in VTE risk prediction, without additional cost to health systems.