ObjectiveVenous thromboembolism (VTE) recurrence is a major concern after a first symptomatic episode, potentially impacting survival and healthcare needs in community, hospital and rehabilitation settings. We evaluated the association of D-Dimer positivity after oral anticoagulant therapy (OAT) discontinuation with VTE recurrence. MethodsPubMed, Web of Science, Scopus and EMBASE databases were systematically searched. Differences were expressed as Odds Ratio (OR) with 95% confidence intervals (95%CI). Pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and summary ROC (sROC) curve were calculated. ResultsTwenty-six articles on 10,725 VTE patients showed that the absolute risk of recurrence was 16.1% (95%CI: 13.2%-19.5%) among 4,049 patients with a positive D-Dimer and 7.4% (95%CI: 6.0%-9.0%) in 6,676 controls (OR: 2.1, 95%CI: 1.7-2.8, P<0.001), with an attributable risk of 54.0%. sROC curve of the association between positive D-Dimer and recurrence showed a diagnostic AUC of 63.8 (95%CI: 60.3-67.4), with a pooled sensitivity of 54.3% (95%CI: 51.3%-57.3%), specificity of 64.2% (95%CI: 63.2-65.1), PLR of 1.53 (95%CI: 1.37-1.72), and NLR of 0.71 (95%CI: 0.60-0.84). Subgroup and meta-regression analyses suggested that a positive D-Dimer may have a higher discriminatory ability for patients with provoked events, confirmed by better pooled diagnostic indexes for recurrence and a diagnostic AUC of 70.6 (95%CI: 63.8-77.4). Regression models showed that the rate of OAT resumption after the evidence of D-Dimer positivity was inversely associated with VTE recurrence (Z-score: -3.91, P<0.001). ConclusionsD-Dimer positivity after OAT may identify VTE patients at higher risk of recurrence, with a better diagnostic accuracy for provoked events.