Abstract: Objective To investigate the efficacy of labetalol-nifedipine combination therapy in patients with hypertensive disorders of pregnancy and its associated risk factors. Methods A total of 207 patients with hypertensive disorders of pregnancy admitted to the Department of Obstetrics of Dongyang People's Hospital between January 2020 and December 2024 were enrolled in this study. A retrospective analysis was conducted based on their clinical data. All patients received treatment with labetalol combined with nifedipine in addition to conventional care. Data on blood pressure parameters before and after treatment and pregnancy outcomes were collected via the electronic medical record system. According to the efficacy evaluation criteria, patients were categorized into a responsive group (n= 168) and a non-responsive group (n= 39). Factors associated with the treatment response of the combination therapy were analyzed. Results The overall response rate among the 207 patients was 81.16%. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured before delivery were significantly lower than those before treatment (P＜0.05). Statistically significant differences were observed between the two groups regarding age, disease severity, baseline SBP and DBP, co-morbid gestational diabetes mellitus, and comorbid hypothyroidism (P＜0.05). Univariate analysis indicated that age, disease severity, baseline SBP and DBP, co-morbid gestational diabetes mellitus, and co-morbid hypothyroidism were significantly associated with treatment efficacy (P＜0.05). Multivariate Logistic regression analysis revealed that age ≥ 35 years, disease severity, co-morbid gestational diabetes mellitus, and co-morbid hypothyroidism were independent risk factors affecting treatment outcomes (P＜0.05). Baseline SBP and DBP did not demonstrate an independent effect, potentially due to collinearity with disease severity (P＞0.05). Conclusion The labetalol-nifedipine combination therapy demonstrates a favorable clinical response rate in the treatment of hypertensive disorders of pregnancy, via the dual-pathway synergistic mechanism of α/β receptor blockade and calcium channel inhibition. However, a small subset of patients exhibits a limited response to the therapy due to factors such as age, disease severity, and specific comorbidities. Personalized interventions should be emphasized for these high-risk populations with suboptimal responses.