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Platelets contain abundant microRNAs (miRs) that regulate gene expression and protein synthesis and may reflect platelet activation. We assessed platelet levels of miR-223, miR-126, and miR-22 in 82 patients with essential hypertension and 28 healthy individuals, using real-time reverse transcription polymerase chain reaction, and evaluated their relation with the patients' clinical profile. Hypertensives had significantly lower platelet miR-22 and miR-223 levels (97.6 ± 170.3 in hypertensives versus 193.8 ± 228.9 in normotensives, p = 0.011, for miR-22; 91.3 ± 154.1 in hypertensives versus 189.9 ± 266.3 in normotensives, p = 0.022, for miR-223). Significant differences in platelet miR levels were also observed between hypertensives who had cardiovascular disease and those who did not (4.1 ± 3.6 versus 75.1 ± 85.2 for miR-126, 24.3 ± 62.9 versus 122.8 ± 187.9 for miR-22, and 10.1 ± 10.4 versus 119.3 ± 169.0 for miR-223, respectively; p < 0.001 for all). In addition, we found a significant negative correlation with systolic blood pressure (SBP) (r = -0.43, p < 0.001, for miR-22; r = -0.47, p < 0.001, for miR-223 in hypertensives; and r = -0.54, p < 0.001, for miR-126). Finally, receiver operating characteristic analysis showed that platelet miR levels were also strong prognostic markers for cardiovascular disease in these patients. In conclusion, platelet miR-22 and miR-223 levels are reduced according to the hypertension status and they are negatively correlated with SBP levels. Platelet miR levels are also related to the presence of overt cardiovascular disease in this population. Further studies are needed to elucidate the exact role of platelet miRs in platelet function and their utility as novel biomarkers of atherothrombotic risk in those patients.