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To provide an overview of the prothrombin 20210A mutation, its effects on the incidence of venous thromboembolism (VTE) in users of oral contraceptive therapy (OCT), and screening recommendations for the primary care practice setting.Several databases, including MEDLINE, EMBASE, BIOSIS, Cochrane Library, and SciSearch, were searched for articles published between 1996 and 2003. An integrative review of studies addressing prothrombin 20210A was done using available case-series and case-control studies. No randomized controlled trials on prothrombin 20210A were available in the literature from the years searched.Prothrombin 20210A increases the risk of developing a VTE for those who carry the genetic mutation. The presence of either concomitant circumstantial factors (e.g., surgery or immobilization) or a combination of genetic factors (e.g., factor V Leiden and prothrombin 20210A) raises the frequency of VTEs to an even greater extent. The risk increases exponentially in users of OCT. Screening guidelines for the use of OCT in prothrombin 20210A carriers remain unclear due to the paucity of empirical evidence related to the topic.Practitioners caring for a prothrombin 20210A carrier should maintain a high degree of suspicion with even vague signs or symptoms of a possible VTE. Practitioners should consider completing a full diagnostic workup for VTE on that patient, particularly if that patient is taking OCT. Until evidence becomes available as to the best anticoagulation practice after an initial or recurrent VTE in a prothrombin 20210A carrier, standard treatment guidelines for anticoagulation should be followed.