BACKGROUND: Extended duration postoperative thromboprophylaxis is suggested by clinical practice guidelines after any cancer-related major abdominal surgeries. However, recent evidence reported relatively low rates of symptomatic venous thromboembolism (VTE) after colorectal cancer surgeries, suggesting the need of a careful risk-benefit assessment in this setting. METHODS: This is a pre-planned post-hoc analysis of the PERIOP-01 trial which compared extended to standard thromboprophylaxis in patients undergoing surgical resection of localized colorectal cancer. Subgroup analyses were performed based on different baseline characteristics. The primary efficacy and safety outcomes were major VTE and clinically relevant bleeding events, respectively. RESULTS: A total of 614 patients were included in the modified intention-to-treat analysis (307 patients in each group). Major VTE events occurred in 2 % and 1 % of the extended and standard-duration thromboprophylaxis groups, respectively. Clinically relevant bleeding events occurred in 3 % of each group. No specific characteristics were found to be associated with a decreased incidence of major VTE among patients receiving extended thromboprophylaxis. Patients with colon cancer resection receiving extended thromboprophylaxis were at an increased risk of clinically relevant bleeding (HR 2.57, 95%CI 1.25-5.30). Other characteristics that may be associated with an increased incidence of bleeding included age (≥75) (HR 2.37, 95%CI 0.47-11.98) and sex (HR 2.13, 95%CI 0.20-23.17). CONCLUSIONS: In the PERIOP-01 trial, extended thromboprophylaxis did not reduce the incidence of major VTE in any subgroups of patients. However, this strategy may be associated with an increased incidence of bleeding among patients with colon cancer, and perhaps among male and elderly patients.