Dual antiplatelet therapy with aspirin and a platelet adenosine diphosphate P2Y(12) receptor blocker reduces the risk of major adverse cardiovascular events following percutaneous coronary intervention or an acute coronary syndrome. Clopidogrel is the most widely used P2Y(12) receptor blocker, but has suboptimal speed of onset of action and maximal platelet inhibition, as well as variability in the inhibition of platelet aggregation achieved. Therefore, novel P2Y(12) receptor blockers have been developed to address these limitations, including prasugrel and ticagrelor. This article describes the pharmacokinetic and pharmacodynamic evaluation of ticagrelor, which has been demonstrated to have significantly faster onset, faster offset, greater maximal inhibition of platelet aggregation and less variability in response compared with clopidogrel. These detailed Phase II data helped guide the design of the large landmark clinical trial Platelet Inhibition and Patient Outcomes (PLATO; n = 18,624 patients with acute coronary syndrome) in which ticagrelor was associated with a 16% relative risk reduction in the primary composite end point of cardiovascular death, myocardial infarction or stroke at 12 months (9.8 vs 11.7%; hazard ratio: 0.84; 95% CI: 0.77-0.92; p < 0.001). Ongoing trials are evaluating the clinical value of individualizing therapy according to on-treatment residual platelet activity, genetic polymorphism (loss-of-function allele status) and by improved safety/efficacy risk stratification.