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Abstract Background Point‐of‐care (POC) International Normalized Ratio (INR) measurement provides efficient monitoring of warfarin therapy; however, its reliability may be affected in patients with anemia, such as those with sickle cell disease (SCD). Objectives To evaluate the correlation of POC‐INR to clinical laboratory INR (CL‐INR) in SCD and use of a correction factor. Patient/Methods In this retrospective study, the accuracy of POC‐INR compared to CL‐INR was evaluated in a cohort of patients with SCD and in a non‐SCD Black cohort. Results Despite the difference in anemia, the SCD cohort showed a similar percentage of in‐range POC‐INR values as observed in the non‐SCD cohort (37% vs 42%). The SCD cohort was randomly divided to form discovery and validation cohorts. In the discovery cohort, 86% of POC‐INRs were in range when the POC‐INRs were ˂4.0, but only 24% were in range if POC‐INRs were ≥4.0. A linear regression of CL‐INR versus POC‐INR for POC‐INR values ≥4.0 yielded a coefficient of 0.72 (95% confidence interval, 0.69‐0.75); Multiplying POC‐INR by this correction factor, rounded to 0.7 for ease of use in clinical practice, improved the proportion of in‐range POC‐INR values ≥4.0 from 24% to 100% in the SCD discovery cohort and from 19% to 95% in the SCD validation cohort. Similar findings applied to analyses of the non‐SCD cohort. Conclusions POC‐INR and CL‐INR in patients with SCD are similar when POC‐INR is <4.0, and the accuracy of POC‐INR values ≥4.0 can be improved by applying an institution‐specific correction factor.