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Objective: To observe the efficacy of different combinations of antihypertensive drugs in patients with nocturnal hypertension (NH), and provide reference for clinical work. Methods: A cross-sectional study was used to collect clinical data of NH patients diagnosed through ambulatory blood pressure monitoring during physical examinations at the First Affiliated Hospital of Hunan University of Medicine from January 2021 to December 2022. According to the different motheds of medication treatment for patients, NH patients were divided into single-drug group, dual-drug group and multi-drug group.Angiotensin converting enzyme inhibitor (ACEI)/ angiotensin Ⅱ receptor antagonist (ARB) or calcium antagonist was used in single-drug group, ACEI/ARB combined with calcium antagonist were used in double-drug group, and any three or four combinations of ACEI/ARB, calcium antagonists, β-blockers and diuretics were used in multi-drug group. The clinical data of the three groups of patients were analyzed and compared. Results: There were 829 patients with NH, including 294 cases (35.46%) in single-drug group, 400 cases (48.25%) in dual-drug group and 135 cases (16.29%) in multiple-drug group. After 6 months of drug treatment, the nocturnal systolic blood pressure (NSBP) and nocturnal diastolic blood pressure (NDBP) of patients in single-drug group, dual-drug group and multi-drug group showed significant differences compared to before treatment (P＜0.05)，among them, the NSBP and NDBP of patients in dual-drug group were significantly lower than those in single-drug group and multi-drug group, but there was no significant difference between the latter two groups (P＞0.05). The decreases in NSBP and NDBP in dual-drug group (21.75%, 20.06%) were greater than those in single-drug group (17.60%, 15.26%) and multi-drug group (18.23%, 16.51%, P＜0.05), respectively. Conclusion: All three motheds of medication treatment can effectively control nocturnal blood pressure, but ACEI/ARB combined with calcium antagonist are more effective in lowering nocturnal blood pressure.