OBJECTIVES: Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder characterized by thrombosis and pregnancy morbidity. Although PAPS is distinct from systemic lupus erythematosus (SLE), the two conditions share clinical features and susceptibility genes. Progression from PAPS to SLE is well recognized. However, risk factors for this transition are poorly understood. We aimed to identify predictors of progression to SLE in patients with PAPS. METHODS: A longitudinal single-centre study was conducted at Hokkaido University Hospital from 1990 to 2021. Baseline characteristics, including clinical features, laboratory data, and antiphospholipid antibody profiles, were compared between patients who progressed to SLE (SLE group) and those who did not (non-SLE group). RESULTS: Among 64 patients diagnosed with PAPS at baseline, nine (13.8%) progressed to SLE over a mean follow-up duration of 9 years (incidence rate, 1.61 per 100 person-years). At the time of the diagnosis of PAPS, the SLE group had a higher prevalence of phosphatidylserine-dependent antiprothrombin antibody (aPS/PT) and anti-dsDNA antibodies compared to the non-SLE group. Other clinical findings, autoantibody profiles, and serum complement levels were similar between the two groups. Multivariate Cox analysis showed that aPS/PT IgG was significantly associated with SLE development (hazard ratio: 10.3, 95% confidence interval: 1.13-92.6, P = .04). CONCLUSIONS: aPS/PT IgG may be a predictive factor for new-onset SLE in patients with PAPS, suggesting its utility in guiding risk stratification and monitoring strategies for these patients.