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<p><b>Background:</b> Scarce data are available on hemoglobin and platelet in relation to coronary artery spasm (CAS) development. We sought to determine the roles that high-sensitivity C-reactive protein (hs-CRP), hemoglobin and platelet play in CAS patients.</p><p><b>Methods: </b>Patients (337 women and 532 men) undergoing coronary angiography with or without CAS but without obstructive coronary artery disease were evaluated during a 12-year period.</p><p><b>Results:</b> Among women with high hemoglobin levels, the odds ratios (OR) from the lowest (&#60;1 mg/l) to the highest tertiles (&#62;3 mg/l) of hs-CRP were 1.21, 2.15, and 5.93 (<i>p</i>=0.009). In women with low hemoglobin levels, an elevated risk was found from the middle to the highest tertiles of hs-CRP (OR 0.59 to 3.85) (<i>p</i>=0.004). This relationship was not observed in men. In men, platelet count was the most significant risk factor for CAS (<i>p</i>=0.004). The highest likelihood of developing CAS was found among women with the highest hs-CRP tertile and low platelet counts (OR 8.77; 95% confidence interval [CI] 2.20-35.01) and among men with the highest hs-CRP tertile and high platelet counts (OR 4.58; 95% CI 0.48-43.97). Neither hemoglobin level nor platelet count was associated with frequent recurrent angina in both genders with CAS whereas death and myocardial infarction were rare.</p><p><b>Conclusions:</b> There are positive interactions among hs-CRP, hemoglobin and platelet in women with this disease, but not in men. While hemoglobin is a modifier in CAS development in women, platelet count is an independent risk factor for men. Both women and men have good prognosis of CAS.</p>