Aims <p>The primary objective of this study was to determine whether concomitant therapy with ticagrelor and rosuvastatin affects rosuvastatin plasma concentrations in patients receiving rosuvastatin 40 mg/day after myocardial infarction.</p> Methods <p>We included 93 patients who had experienced a myocardial infarction and were receiving high-dose rosuvastatin 40 mg/day and a P2Y12 receptor antagonist, either ticagrelor, prasugrel or clopidogrel. We used liquid chromatography with tandem mass spectrometry to measure rosuvastatin plasma concentrations after liquid–liquid extraction.</p> Results <p>Rosuvastatin plasma concentrations (9.7 ng/mL) were approximately twice as high in patients receiving ticagrelor therapy as in those receiving prasugrel (5.1 ng/mL, <i>p</i> &lt; 0.001) or clopidogrel (5.0 ng/mL, <i>p</i> = 0.009), and ticagrelor was an independent factor influencing rosuvastatin concentrations. In addition, creatinine levels were associated with increased rosuvastatin concentrations (<i>p</i> = 0.039).</p> Conclusion <p>Our results suggest an important pharmacokinetic interaction between ticagrelor and rosuvastatin, leading to approximately two-fold higher rosuvastatin plasma concentrations in those receiving concomitant ticagrelor than in those receiving prasugrel or clopidogrel. The association is significant and independent of other potential factors influencing rosuvastatin levels, indicating its potential clinical relevance.</p>