OBJECTIVES: Comparative effectiveness research identifies superior clinical devices or treatments through head-to-head comparisons.  This study describes the use of an innovative framework to assess the quality and safety of two INR Point of Care devices. METHODS: Patients enrolled in the hematology Anticoagulation Management Service provided three INR measures: one venous sample analyzed by our lab (considered the standard measure), one fingerstick analyzed by the Hemochron Signature Elite POC device and another fingerstick by the Coaguchek XS Plus.  Agreement between INR values from each device and the lab was assessed.  Agreement was achieved when the INR measures were predicted by a novel, validated method to lead to the same clinical decision.  Differences in agreement between the POC devices and the lab were assessed using McNemar’s test of paired proportions.  RESULTS: Ninety-nine subjects were enrolled into the study.  There was significantly less difference between INR values from the Coaguchek XS device and the lab compared to the Hemochron device (average absolute difference = 0.24 vs 0.41 p<0.05).  The Hemochron device tended to report both high and low INR values were within the target range when the laboratory said otherwise.  Consequently, the Hemochron device was significantly more likely to lead to a different clinical decision than the core laboratory compared to the Coaguchek XS (30% vs. 18%, respectively; RR: 1.7, 95% CI: 1.1-2.4, P=0.007). CONCLUSIONS: Comparative effectiveness analysis can provide essential information to make informed decisions when selecting medical devices to be utilized in clinical practice.  The analytic framework in this comparative effectiveness analysis demonstrated the Coaguchek XS device to have a significantly higher level of agreement with the core lab compared to the Hemochron device.   This analysis led our institution to select the Coaguchek XS for use in our anticoagulation clinics on the basis of a superior quality and safety profile.