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<h4>Purpose</h4>A systematic review and meta-analysis was conducted comparing the presence of anti-phospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis of antiphospholipid syndrome, who experienced at least two implantation failures following in vitro fertilization and embryo transfer (IVF-ET), and either women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET.<h4>Methods</h4>Systematic search of the literature and meta-analysis of the relevant studies studying presence of antiphospholipid antibodies in women experiencing at least two implantation failures in IVF-ET as compared to either women who had a successful implantation after IVF-ET or/and women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. Six hundred ninety-four published reports were retrieved; 17 of them fulfilled the inclusion criteria set.<h4>Results</h4>Presence of either any type of anti-phospholipid or anticardiolipin antibodies or lupus-anticoagulant in women experiencing at least two implantation failures in IVF-ET was associated with increased implantation failure compared to women who had a successful implantation after IVF-ET (relative risk, RR: 3.06, 5.06 and 5.81, respectively). Presence of either anticardiolipin or lupus-anticoagulant or anti-beta2 glycoprotein-I or anti-phosphatidylserine antibodies in women experiencing at least two implantation failures in IVF-EΤ was associated with increased implantation failure compared to unselected healthy fertile women with no history of IVF-ET (RR:13.92, 6.37, 15.04 and 164.58, respectively).<h4>Conclusion</h4>The prevalence of antiphospholipid antibodies, particularly that of anti-beta2 glycoprotein-I and anti-phosphatidylserine antibodies, in women experiencing at least two implantation failures in IVF-ET without diagnosis of antiphospholipid syndrome is significantly greater than either in women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET.<h4>Trial registration number</h4>PROSPERO ID: CRD42018081458.