Protein Z (PZ) is a vitamin K-dependent protein involved in the down-regulation of coagulation by forming a complex with the protein Z-dependent protease inhibitor. The complex inhibits the activated factor X on phospholipid surface. Presence of anti-PZ (aPZ) antibodies was first described in women with pathological pregnancies but the significance of aPZ antibodies in other pathological situations was poorly studied. In this work we analyzed the frequency of aPZ antibodies in a series of 86 consecutive patients with anticardiolipin (aCL) antibodies and studied the association of aPZ with other antiphospholipid (aPL) antibodies [lupus anticoagulant (LAC) and anti-ss2GP-1 antibodies] and the clinical signification of these aPZ antibodies in term of thrombosis or fetal loss. Anti-PZ antibodies (IgG and IgM) were detected using commercially available ELISA assays. The frequency of aPZ antibodies was 40.7% in the patient group versus 6.8% in a group of 59 healthy volunteers (p < 0.0001). The frequency of aPZ antibodies significantly increases (p < 0.05) in patients with a double or triple positivity of aPL antibodies and a higher frequency of aPZ antibodies was observed in patients with LAC (57.7%) than in patients without LAC (25.6%, p = 0.02). There were no significant differences in aPZ antibodies frequency between patients with and without thrombotic events. Interestingly, among the 8 women with recurrent foetal losses, aPZ antibodies were observed in 7 cases, in agreement with previous observations suggesting that aPZ antibodies may be associated with obstetrical complications.