The association between antiphospholipid antibodies (aPL) and clinical events is stronger with a positive lupus anticoagulant (LA) test, higher anticardiolipin antibody (aCL) titers, and/or higher anti-beta(2)-glycoprotein-I antibody (abeta( 2)GPI) titers. The objective of this study was to determine the clinical characteristics of persistently high-titer (> or =80 U) aCL-positive patients compared with those with persistent moderate aCL titers (40-79 U). Second, we analyzed whether high-titer abeta(2)GPI test adds predictive information in persistently moderate-to-high titer aCL-positive patients. In this cross-sectional study, the primary analysis compared the clinical and aPL characteristics of 58 patients with at least two moderate-titer aCL results to another 85 patients with at least two high-titer aCL results. In the secondary analysis of patients with at least two abeta(2)GPI test results, we compared 29 patients with 'aCL 40-79 U and abeta( 2)GPI < 80 U' profiles with 8 patients with 'aCL 40-79U and abeta(2)GPI > or = 80 U', and also compared 27 patients with 'aCL > 80 U and abeta(2)GPI < 80 U' with 32 patients with 'aCL > 80 U and abeta(2)GPI > or = 80 U'. Although aPL-related vascular and pregnancy events were similar between the moderate- and high-titer aCL groups, the number of patients with positive LA tests (RR 2.06, CI 1.38-3.08, p < 0.01) and with at least one non-criteria aPL manifestation (RR 1.66, CI 1.20-2.30, p = 0.0005) were significantly higher in the high-titer aCL group. While magnetic resonance imaging (MRI) white matter changes were statistically more common in the high-titer aCL group (RR 2.03, CI 1.04-3.94, p = 0.02), there was a trend towards increased prevalence of livedo reticularis, cardiac valve disease, and cognitive dysfunction occurring in the high-titer aCL group. The secondary analysis showed that MRI white matter changes, cardiac valve disease, and cognitive dysfunction were proportionally more common in the high-titer abeta( 2)GPI groups, suggesting a linear relationship between non-criteria aPL manifestations and aPL titers. Our results suggest that patients with high aCL titers, compared with those with moderate titers, are more likely to have a positive LA test and a higher prevalence of non-criteria aPL manifestations. Furthermore, high-titer abeta(2)GPI positivity may further increase the prevalence of non-criteria aPL manifestations in moderate- or high-titer aCL-positive patients.