Background: Heparin-induced thrombocytopenia (HIT) is an infrequent but serious complication of heparin therapy. HIT is a hypercoagulable state and life-threatening thrombotic complications often occur. Diagnosis of HIT is complicated by the non-specific nature of its signs and the operating characteristics of the antibody test used to confirm its presence. Furthermore, the direct thrombin inhibitors (DTI) available to treat HIT are expensive and may increase bleeding risks. Objective: To evaluate the cost-effectiveness of four treatment approaches for patients receiving heparin who develop suspected HIT. These strategies are: 1. continue heparin without testing antibody levels (HEP); 2. test antibody levels, continue heparin while test is pending, and switch to a DTI for a positive result (TEST+HEP); 3. test antibody levels, switch to a DTI while test is pending, and switch back to heparin for negative result (TEST+DTI); 4. switch to a DTI without testing antibody levels (DTI). Methods: We performed a cost-effectiveness analysis using standard decision analytic methods. Parameter estimates were obtained from literature. Costs of drug treatment, testing, and adverse events were tallied; effectiveness was captured as quality adjusted life expectancy (QALE). The effects of parameter uncertainty and variability on model results were evaluated through sensitivity analyses. Results: HEP had the lowest cost ($1670) and resulted in the lowest QALE (11.71 years). Relative to HEP, TEST+HEP increased QALY by 0.053 quality adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $11,500 per QALY. TEST+DTI saved an additional 0.0035 QALYs compared to TEST+HEP and had an ICER of $74,300 per QALY. The ICER for DTI compared to TEST+DTI was > $11 million. These results were most sensitive to assumptions about the probability that patients presenting with thrombocytopenia actually have HIT. Thrombosis rates among HIT patients left on heparin, relative rates of bleeding on DTIs versus heparin, and mortality rates for patients with bleeds were also important parameters. Conclusions: In patients with suspected HIT, a treatment strategy of testing antibody levels, continuing heparin while test results are pending, and switching to a DTI for positive results (TEST+HEP) appears very cost-effective. TEST+DTI may be on the margin of acceptable cost-effectiveness. These results are relevant to clinicians facing difficult decisions surrounding the treatment of patients with suspected HIT.