Abstract Objectives To assess the prevalence and clinical significance of autoantibodies against lysobisphophatidic acid (aLBPA) in patients with APS. Methods We conducted a retrospective analysis involving 91 patients with persistent conventional aPLs: 60 patients with at least one clinical event of APS (symptomatic group) and 31 without (asymptomatic group), as well as 33 aPL-negative controls. Detection of aLBPA in serum samples was performed using an enzyme-linked immunosorbent assay (ELISA) specifically designed for this study. Results The prevalence of aLBPA is significantly higher in patients with persistent aPL than that of the control group (P < 0.0001). Among patients with persistent aPL, our findings reveal a significantly higher prevalence of aLBPA in asymptomatic patients compared with their symptomatic counterparts (P = 0.027). Notably, patients positive for IgG aPL alone demonstrated a greater likelihood of presenting clinical events suggestive of APS. Conclusion The combined assay of aLBPA and conventional aPL could be used to stratify patients with persistent aPL. This combined approach could serve as a valuable tool in the management of this complex autoimmune disease, particularly in guiding decisions regarding the initiation of primary thromboprophylaxis in asymptomatic patients with persistent aPL.