Venous thromboembolism (VTE) is an increasingly frequent complication of solid tumors and hematological malignancies, significantly contributing to morbidity and mortality. In patients with acute cancer-associated VTE, therapeutic anticoagulation with direct oral factor Xa inhibitors (DXIs) or low-molecular-weight heparin (LMWH) for 3 to 6 months is recommended by clinical practice guidelines based on randomized controlled trials. Although extended secondary VTE prophylaxis should be considered in patients with persisting active cancer, the type, intensity, and duration of continued anticoagulation have not been rigorously studied until recently. In non-cancer patients, low-dose DXIs (apixaban 2.5 mg BID or rivaroxaban 10 mg OD) are the preferred options to prevent recurrent VTE beyond the first 6 months of treatment. The recently published API-CAT trial compared low-dose with full-dose apixaban for extended secondary VTE prophylaxis in 1,766 patients with active cancer. Over a 12-month period, low-dose apixaban was associated with similar efficacy, but significantly improved safety compared with full-dose apixaban, with cumulative incidence rates of recurrent VTE and major or clinically relevant non-major bleeding of 2.1% versus 2.8% (adjusted subhazard ratio [sHR]: 0.76; 95% confidence interval [CI]: 0.41–1.41; p < 0.001 for noninferiority) and 12.1% versus 15.6% (adjusted sHR: 0.75; 95% CI: 0.58–0.97; p = 0.03 for superiority), respectively. Based on these findings, extended secondary VTE prophylaxis with low-dose DXIs, preferably apixaban 2.5 mg BID, is proposed for most patients with persisting active cancer. To facilitate informed decision-making in clinical practice, we provide an expert consensus on criteria that either justify cessation of anticoagulation or require continued full-dose anticoagulation.