Genetic variants among individuals have been associated with ineffective control of hypertension. Previous work has shown that hypertension has a polygenic nature, and interactions between these loci have been associated with variations in drug response. Rapid detection of multiple genetic loci with high sensitivity and specificity is needed for the effective implementation of personalized medicine for the treatment of hypertension. Here, we used a cationic conjugated polymer (CCP)-based multistep fluorescence resonance energy transfer (MS-FRET) technique to qualitatively analyze DNA genotypes associated with hypertension in the Chinese population. Assessment of 10 genetic loci using this technique successfully identified known hypertensive risk alleles in a retrospective study of whole-blood samples from 150 patients hospitalized with hypertension. We then applied our detection method in a prospective clinical trial of 100 patients with essential hypertension and found that personalized treatment of patients with hypertension based on results from the MS-FRET technique could effectively improve blood pressure control rate (94.0% versus 54.0%) and shorten the time duration to controlling blood pressure (4.06 ± 2.10 versus 5.82 ± 1.84 days) as compared with conventional treatment. These results suggest that CCP-based MS-FRET genetic variant detection may assist clinicians in rapid and accurate classification of risk in patients with hypertension and improve treatment outcomes.