Prasugrel results in greater platelet inhibition compared to clopidogrel which may prolong the time to platelet P2Y(12) receptor function recovery following drug cessation after loading dose (LD) administration. This randomized study assessed the time to recovery of platelet function in patients with coronary artery disease after a LD of prasugrel or clopidogrel. Enrolled patients (n = 21) received either prasugrel (30 mg or 60 mg) or clopidogrel (600 mg) in preparation for coronary angiography. Platelet function was assessed by the VerifyNow P2Y12 assay, Multiplate and LTA at baseline and over time (1, 3, 5, 7, 9, and 11 days) post-LD treatment. Recovery of platelet function was defined as occurring on the first day that P2Y12 reaction units were <=60 below pre-drug values and remained in this range. The relationship between platelet inhibition at 24 h post-LD to time of recovery was also evaluated. Recovery of platelet function occurred from days 3-7 for clopidogrel-treated subjects, by day 7 for patients treated with prasugrel 30 mg and from days 7-9 for patients treated with prasugrel 60 mg. Time for platelet function to return to baseline was independent of treatment assignment, reflecting instead the extent of platelet inhibition at 24 h post-LD (correlation coefficient = 0.81, p < 0.001), which was greater following a prasugrel LD.Prasugrel-treated subjects require a longer time for recovery compared with clopidogrel due to greater post-LD platelet inhibition. Platelet function testing after cessation of P2Y(12) receptor blockers may prove useful to guide the timing of surgical procedures (clinicaltrials.gov identifier: NCT01107899).