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Venous thromboembolism (VTE) is associated with an elevated short-term cancer risk, but data on the long-term risk are conflicting. The mechanisms linking patients with VTE to elevated long-term cancer risk remain largely unknown.

To investigate long-term cancer risk after VTE and whether this risk pertained predominantly to cancers sharing risk factors with VTE.

Using nationwide Danish registries, we followed patients with first-time VTE (1996-2022) until cancer diagnosis, death, emigration, or December 31, 2022, whichever occurred first. We used the Aalen-Johansen estimator to compute cumulative cancer incidence, treating death as a competing event. Standardized incidence ratios (SIRs) compared observed events with expected events based on general population rates. We analyzed cancer incidence overall and by site-specific and etiology groups for smoking-, obesity-, alcohol-, hormone-, and infection-related cancers, and "all other" cancers.

We followed 138,049 patients for a median of 5.5 years. The 1-year cancer risk was 4.0%. The 1-year SIR was 3.45 (95% CI, 3.36-3.55), then ranged from 1.09 to 1.16 over 20 years of follow-up, reaching 1.00 (95% CI, 0.90-1.11) thereafter. SIR was elevated in all cancer groups within 1 year and afterward, but was driven by site-specific cancers often related to smoking, obesity, and alcohol (lung, pharynx, larynx, esophagus, stomach, liver, pancreas, and colon), as well as hematological cancers.

Compared with the general population, patients with VTE had an increased cancer risk for up to 20 years. Shared risk factors, such as lifestyle-related factors and genetic predisposition, may contribute to this increased risk.