PURPOSE: To investigate how genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) influence hypertension (HT) control with angiotensin-converting enzyme inhibitor drugs (ACEI). METHODS: A case-control, cross-sectional population-based nested study (n=1514) included hypertensive patients treated with ACEI drugs, either alone or with other antihypertensive drugs. We differentiated between those who did not control their HT (cases) with those who did (controls). Each group's characteristics were compared to determine the risk of non-controlled HT associated with RAAS polymorphisms by adjusting for different variables. RESULTS: rs11571074 obtained an ORa of 5.26 for T/T (1.25-20). rs5945377 obtained an ORa 16.16 (1.61-162.62) for genotypes G/G-G/C. rs909383, rs275649 and rs4681444 obtained an ORa of 4.00 (1.19-14.28), 5.89 (1.53-25) and 3.89 (1.53-25) when genotypes C/C and A/A were expressed for the first and for the other two, respectively. For rs2272089, rs13117325 and rs11099680, a higher non-control risk was seen in A/G-G/G carriers (ORa: 4.9 (1.3-18.3); ORa: 3.7 (1.0-13.4); ORa: 6.5 (1.7-24.7). Finally, rs6535598 obtained an ORa of 10.4 (1.2-92.9) in T/T carriers. CONCLUSIONS: Although this study shows a possible association of polymorphisms of RAAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.