Scope: We investigate the postprandial modulation of cardiovascular‐related microRNAs elicited by extra virgin olive oil (EVOOs) containing different levels of their own polyphenols. Methods and results: It is randomized, postprandial, parallel, double‐blind study. Twelve healthy participants consumed 30 mL of EVOO containing low (L‐EVOO; 250 mg total phenols kg−1 of oil), medium (M‐EVOO; 500 mg total phenols kg−1 of oil), and high (H‐EVOO; 750 mg total phenols kg−1 of oil) enriched EVOOs. Postprandial plasma microRNAs levels are analyzed by real‐time quantitative PCR. The results show that L‐EVOO intake is associated with decreased let‐7e‐5p and miR‐328a‐3p levels and increased miR‐17‐5p and miR‐20a‐5p, concentrations. M‐EVOO decreases plasma let‐7e‐5p and increases miR‐17‐5p, miR‐20a‐5p, and miR‐192‐5p levels. Finally, H‐EVOO decreases let‐7e‐5p, miR‐10a‐5p, miR‐21‐5p, and miR‐26b‐5p levels. Conclusion: During the postprandial state, the levels of let‐7e‐5p decrease with EVOO regardless of polyphenol content suggesting a general response to the fatty acid composition of EVOO or/and the presence of at least 250 mg polyphenol kg−1 olive oil. Moreover, the miR‐17‐92 cluster increases by low and medium polyphenol content suggesting a role in fatty acid metabolism and nutrient sensing. Thus, postprandial modulation of circulating microRNAs levels could be a potential mechanism for the cardiovascular benefits associated with EVOO intake.