AIMS This study characterizes the influence of genotype at two loci on warfarin response after arthroplasty. METHODS 121 postarthroplasty patients given warfarin thromboprophylaxis were reviewed for international normalized ratio (INR) values on the first three days postoperatively. Significant differences among genotypes in INR values on each of the first three postoperative days were assessed. RESULTS Wild-type patients at both loci (∼23% of patients) had yet to reach therapeutic INR (1.5-2.0) by postoperative day three more frequently than those with a mutation conferring hyper-responsiveness (61% vs. 30%; P ≤ .01). CONCLUSIONS Wild-type patients are not anticoagulated in a sufficiently prompt manner after arthroplasty.