Recurrent pregnancy loss (RPL) is a major problem of women's health and it is regulated by polygenes. Recently, a promoter variation in annexin A5, named M21ANXA5 haplotype showed the reduced expression of annexin A5 (ANXA5), resulted in thrombophilia-associated obstetric complications. The study aimed to determine the role of M2IANXA5 for RPL in Malaysian Malay women. A total of 238 women who had experienced ~ 2 unexplained RPL and 143 available male partners were recruited for this research, with 360 population controls of healthy Malay individuals. Incidence of M2 carriage and odds ratios were calculated in a) control and patient groups, b) clinically defined subgroupsl and c) timing of pregnancy loss subgroups. Both male and female subjects had similar M2IANXA5 allele frequencies. The carrier rate of M2IANXA5 for the Malay population was 42.2% that compared to RPL Malay resulted in an elevated risk (OR = 1.65), specifically for early fetal losses (gestational weeks 10 - 15). Moreover, exceeding copy numbers of M21ANXA5 alleles seemed to contribute a higher risk in RPL couplesl obtained result was substantiated for couples, where both partners were M2 carriers. This study confirmed the proposed role of M2IANXA5 as a genetically associated thrombophilia predisposition factor for Malaysian Malay RPL.