miR-33a has been described as a key regulator in the initiation and progression of atherosclerosis. However, its role in arterial hypertension (HTA) has not been elucidated. Therefore, the aim of this study was to determine the association between the expression of miR-33a (5p and 3p) and the carotid intima-media thickness (cIMT) in samples of monocytes and serum from hypertensive patients. The miR-33a-5p and miR-33a-3p expression in monocytes and serum from Mexican hypertensive patients were examined by RT-PCR. This study involved 84 subjects (42 normotensive subjects and 42 patients with essential hypertension). Our study revealed that miR-33a-5p expression was significantly upregulated in the monocytes of hypertensive patients compared with the control group (p = 0.001), while miR-33a-3p was significantly downregulated (p = 0.013). miR-33a-5p upregulation [OR: 5.53, 95% CI: 2.01-15.20; p = 0.001], as well as miR-33a-3p downregulation [OR: 3.32, 95% CI: 1.45-7.60; p = 0.004] in monocytes, was associated with an increased risk of developing hypertension. In addition, miR-33a-5p upregulation in hypertensive patients was associated with an increased risk of presenting cIMT [OR: 5.99, 95% CI: 1.10-32.85; p = 0.039]. Moreover, we found no significant differences in the expression of both strands of miR-33a in serum of our patients. Our results showed an upregulation of miR-33a-5p and downregulation of miR-33a-3p in monocytes, these data are associated with cIMT, which could be a risk factor for the development of hypertension. In addition, upregulation of miR-33a-5p in monocytes from Mexican hypertensive patients could be involved in the development of atherosclerosis.