Objective: To investigate the correlation of single-nucleotide polymorphisms of the Multidrug Resistance Gene (MDR) 1C3435T and the human Endothelin Converting Enzyme (ECE-1) gene with the efficacy of irbesartan in primary hypertension. Methods: A total of 186 patients with primary hypertension in our hospital from May 2015 to December 2016 received irbesartan oral medication. The 1C3435T and ECE-1 gene polymorphic sites were detected. Meanwhile, the plasma concentration was measured every hour after taking medicine for 8 h, and the plasma concentration peak was recorded. The systolic and diastolic blood pressures of the patients were recorded before and after treatment. The relationships between the different genotypes and plasma concentrations, as well as the drop of blood pressure, were compared. The antihypertensive effects of different genotypes were also investigated. Results: The distribution frequencies of the 1C3435T CT, TT, and CC genotypes were 37.63%, 34.95%, and 27.42%, respectively, whereas those of the C-338A CA, AA, and CC genotypes were 32.80%, 30.65%, and 36.56%, respectively. The plasma concentration peak, drop of blood pressure, and total effective rate of the 1C3435T TT genotype were significantly higher than those of CT and CC (P<0.05). The corresponding data of CT were significantly also higher than those of CC (P<0.05). Moreover, the plasma drug concentration, drop of blood pressure, and total effective rate of the C-338A CC genotype were significantly higher than those of CA and AA (P<0.05), and the corresponding data of CA were significantly higher than those of AA (P<0.05). Conclusion: During the oral treatment of primary hypertension by irbesartan tablets, the MDR1 1C3435T TT and ECE-1 C-338A CC genotypes can significantly increase the plasma concentration peak and significantly improve the curative effect.