The potential weaknesses of our study are several. First, although we established predefined criteria for study selection, the quality of meta-analysis remains dependent on the quality of the included studies. Four of the 13 reports included in our meta-analysis were retrospective, and all studies were subject to selection or referral bias because patients with unprovoked VTE, a large thrombotic burden, or significant comorbidities are more likely to be referred to specialist centers, included in studies, and described in the literature. Second, the included studies were conducted over different time periods (1980s to 2002), and it is unclear how changing clinical practices and the introduction and uptake of new diagnostic and therapeutic approaches might have influenced referral and treatment patterns. However, sensitivity analyses demonstrated broadly similar odds of VTE recurrence in the cases with FVL and prothrombin G20210A regardless of whether the study was started before or after the median year of commencement of all studies. Third, we could not obtain missing data from all of the studies despite contacting the authors. Finally, VTE is a multifactorial disorder, caused in part by gene-gene and gene-environment interactions, many of which are still poorly defined and understood. Most of the studies included in our meta-analysis were undertaken in European centers, and it is unknown if our findings can be extrapolated to other communities with potentially different genetic and environmental risk factors for VTE.