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<it>Objectives</it>. To define the specificity and positive predictive value of anti‐<it>β</it><inf>2</inf>‐glycoprotein 1 (anti‐<it>β</it><inf>2</inf>GP1) antibodies for the diagnosis of antiphospholipid syndrome (APS). <it>Methods</it>. We determined the presence of anticardiolipin (aCL) antibodies and anti‐<it>β</it><inf>2</inf>‐glycoprotein 1 (anti‐<it>β</it><inf>2</inf>GP1) immunoglobulin (Ig) G and IgM in 191 consecutive sera from 191 patients and reviewed clinical data separately. aCL IgG and IgM were detected separately using commercial ELISA kits. Anti‐<it>β</it><inf>2</inf>GP1 antibodies were detected with an in‐house ELISA using <it>β</it><inf>2</inf>GP1. <it>Results</it>. Seven patients were diagnosed as having APS and 184 as having other diseases. Thirty‐six patients were aCL‐positive and 12 were anti‐<it>β</it><inf>2</inf>GP1‐positive, seven of these 12 were APS patients. The specificity for anti‐<it>β</it><inf>2</inf>GP1 in our population was 97%, with a positive predictive value (PPV) of 58%. Among the aCL‐positive patients, specificity was 90% and PPV 70–87%. <it>Conclusions</it>. This study shows that anti‐<it>β</it><inf>2</inf>GP1 antibodies have a higher specificity and PPV than aCL for APS. The PPV of anti‐<it>β</it><inf>2</inf>GP1 was greater in aCL‐positive than in all patients. We conclude that screening for anti‐<it>β</it><inf>2</inf>GP1 antibodies in aCL‐positive patients increases the specificity and the PPV of aCL testing. In addition, we show that there is no need to screen for anti‐<it>β</it><inf>2</inf>GP1 antibodies in the absence of aCL antibodies and in the absence of strong clinical suspicion of APS.