A clopidogrel loading dose before percutaneous coronary intervention may reduce ischemic events but can increase bleeding risk and result in delayed treatment in patients who subsequently require surgical revascularization. The goal of this study was to examine the dynamics of platelet functional recovery after the common clinical scenario of a single 600-mg loading dose of clopidogrel. Fourteen volunteers were administered clopidogrel 600 mg. Platelet reactivity was measured before exposure, 4 hours after exposure, and then daily for 8 days using the VerifyNow P2Y12 assay. Percentage inhibition (PI) was calculated as the relative change in P2Y12 reaction units from baseline. One day after clopidogrel, the median PI was 39.9% (range 8.5% to 97.7%). Before day 5, the number of days after exposure was significantly but weakly correlated with PI (Pearson's coefficient = 0.45, R2 = 0.20, p = 0.001), while most of the variance in PI on each day of recovery was explained by the PI that was observed the previous day (Pearson's coefficient = 0.95, R2 = 0.92, p <0.001). The decay in PI over time was exponential, with a common ratio of 17% relative reduction per day (95% confidence interval 10% to 23%). Similar findings were observed when the effect of clopidogrel was defined by residual platelet reactivity or by the adenosine diphosphate-prostaglandin E1/iso-thrombin receptor-activating peptide ratio. In conclusion, platelet inhibition on each day after a loading dose varies considerably among subjects. The level of inhibition depends less on the number of days after exposure than on the magnitude of initial inhibition after loading. A strategy of individual platelet function monitoring should be examined in patients requiring cardiac surgery after clopidogrel loading.