To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use. One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ฏ 1, 2, 4 and 6 hours after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 hour after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N=32) as compared with patients not receiving morphine (N=98; PRU= 187 [70-217]) vs 73 [7-187]; p=0.012). In patients with morphine, 1-hour PRU values were similar between study groups (192 [114-236] vs 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-hour PRU values were not significantly different between study groups (69 [8-152] vs 110 [6 - 193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4 and 6 hours after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine. There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.