The CoaguChek XS meter is an international normalized ratio (INR) point-of-care (POC) monitor that has been shown to provide clinically acceptable accuracy. Because of a potential interaction between antiphospholipid antibodies and the reagent used in the prothrombin time INR assay, there is uncertainty as to the reliability of using POC INR monitors in patients with antiphospholipid syndrome (APLS). The study population consisted of 41 patients on warfarin therapy for either APLS (treatment group) or any other indication (control group). All patients had their INR analyzed by the CoaguChek XS meter and a central laboratory. Overall, the mean INR difference between the CoaguChek XS and laboratory in the APLS patients was 0.6772 (P < 0.0001). In APLS patients, when the laboratory INR was less than 2.0, 2.0 to 3.0, 3.1 to 4.0, or greater than 4.0, the CoaguChek XS differed by averages of 0.0636 (P = 0.4111), 0.6903 (P < 0.0001), 1.1417 (P < 0.0001), and 0.9333 (P = 0.0848), respectively. In the control group the overall mean difference was 0.5456 (P < 0.0001). For laboratory INR values of less than 2.0, 2.0 to 3.0, 3.1 to 4.0, and greater than 4.0, the mean differences from the CoaguChek XS were 0.3000 (P = 0.0003), 0.4444 (P < 0.0001), 1.0444 (P = 0.0002), and 1.3500 (P = 0.0236). Our data do support the manufacturer recommendation of comparing laboratory and CoaguChek XS meter INRs in APLS patients because in a subset of patients the 2 methods produced acceptable results, and POC monitoring might be used.