OBJECTIVE: The objective of this study was to investigate the relationship between plasma levels of thrombin-activated fibrinolytic inhibitor (TAFI) and recurrent spontaneous abortion (RSA) in varying conditions of anti-thyroid antibodies (ATA), and to provide appropriate recommendations for RSA prevention. Design: Retrospective case-control study. Setting：Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University. Sample: There were 1068 subjects in this retrospective study, including 402 RSA patients and 666 controls. Methods: Collected case records from the Department of Obstetrics and Gynecology from January 2020 to March 2022 for comparative analysis between cases and controls. Main outcome measures: Patients’ socio-demographic factors, plasma TAFI levels, ATA status, including thyroid peroxidase antibodies (Anti-TPO) and thyroglobulin antibodies (Anti-TG), thyroid function, coagulation function, and so on. Multivariate adjusted conditional logistic regression and restricted cubic spline (RCS) models were applied to evaluate odds ratios (ORs) and their 95% confidence intervals (CIs) between plasma TAFI levels and the risk of RSA under different ATA conditions according to the normal reference range of plasma TAFI levels (24-35ug/ml). Results: Compared to normal TAFI levels (as reference), low TAFI levels (<24ug/ml) had a significantly increased risk of RSA, which was shown in the Anti-TPO positive group (OR, 2.15; 95% CI, 1.221-3.785; P=0.008), Anti-TPO negative group (OR, 1.429; 95% CI, 1.032-1.98; P = 0.032), and Anti-TG positive group (OR, 2.215; 95% CI, 1.265-3.878; P = 0.005). In addition, the RSC model showed that plasma TAFI levels showed a linear negative dose relationship with the risk of RSA. Conclusions: The study indicates that pregnant women with plasma TAFI levels below the normal range, especially those who are ATA positive, are at a higher risk of developing RSA. These findings suggest the need to develop prevention recommendations.