SummaryAnti-phospholipid antibodies (aPL) are autoantibodies associated with both infections and the pathogenesis of certain pregnancy complications. In the latter, but not the former, aPL are dependent on a co-factor, β2 glycoprotein I (β2GPI), which can also be used as an antigen for detection of such aPL in pregnancy. A cross-sectional study was carried out on serum samples from Kumasi, Ghana, to determine the occurrence and β2GPI-dependence of aPL in placental malaria. Anti-cardiolipin, anti-phosphatidylserine and anti-β2GPI enzyme-linked immunosorbent assays (ELISAs) were performed on sera from 103 HIV-non-infected gravid women. Placental malaria, both active and past infection, was diagnosed in 33/103 (32%) based on placental histology. In multiparae, β2GPI-independent IgM antibodies to cardiolipin (P = 0·018) and phosphatidylserine (P = 0·009) were observed, which were most pronounced in past placental malaria infection. In primiparae, no association emerged between aPL and placental malaria. Trends for improved clinical parameters were identified in infected women with levels of anti-cardiolipin beyond the 99th multiple of the median for a healthy, non-malarious population. This study in placental malaria reports parity associations of β2GPI-independent aPL profiles, and does not support a role for β2GPI-dependent aPL. It is of significance in the context of the known parity differences in pregnancy malaria immunity.