To investigate the association between anti-prothrombin IgM and IgG antibodies and recurrent pregnancy loss (RPL) in a cohort of Lebanese women, and their impact on pregnancy outcomes. This was a retrospective case-control study involving 207 women with RPL and 179 age-matched multiparous controls. Quantitative sandwich ELISA assayed anti-prothrombin IgM and IgG antibodies. Univariate and multivariate logistic regression were employed to assess the risk imparted by anti-prothrombin antibodies, while ROC analysis was used to determine their sensitivity and specificity. Our study revealed that women with RPL had significantly higher serum levels of anti-prothrombin IgM and IgG than controls. Univariate regression analysis demonstrated that elevated anti-prothrombin IgM (OR = 1.13; 95% CI = 1.07, 1.19; P < 0.001) and IgG (OR = 1.05; 95% CI = 1.03, 1.08; P < 0.001) were associated with increased RPL risk. Multivariate analysis confirmed these findings, indicating that anti-prothrombin IgM (aOR = 1.13; 95% CI = 1.05, 1.20; P < 0.001) and IgG (aOR = 1.08; 95% CI = 1.05, 1.11; P < 0.001) are independent risk factors. ROC analysis yielded an AUC of 0.720 for IgM and 0.649 for IgG, underscoring their predictive value and offering hope for improved risk assessment and management of RPL. Elevated levels of anti-prothrombin IgM and IgG are significantly associated with RPL, suggesting an autoimmune component to pregnancy loss. These findings highlight the importance of screening for these antibodies in women with unexplained RPL to guide management and therapeutic strategies.