Objective To compare the clinical effects of paricalcitol, cinacalcet, and their combination therapy in managing secondary hyperparathyroidism (SHPT) in hemodialysis patients. Methods A total of 120 SHPT patients were divided into three groups based on their treatment regimen: the paricalcitol group, the cinacalcet group, and the combined therapy group, with 40 patients in each group. The patients were followed for 12 months, and the levels of intact parathyroid hormone(iPTH), serum calcium, and phosphorus were measured at baseline and at the 3rd, 6th, 9th, and 12th month. Cardiovascular events and hospitalization status were recorded. Repeated-measures analysis of variance (ANOVA) was used to compare the changes in biochemical indicators across the three groups, and the chisquare test and multivariate Logistic regression analysis were employed to compare the incidence of cardiovascular events and their related influencing factors. Results After excluding patients with incomplete follow-up, 116 patients were analyzed (38 in the combined therapy group, 39 in the cinacalcet group, and 39 in the paricalcitol group). The cinacalcet group showed a continuous decrease in iPTH, which was significantly lower than the other two groups (P <0.05). The combined group exhibited fluctuating iPTH levels, while the paricalcitol group showed intermediate results. Serum calcium and phosphorus levels in the cinacalcet group were significantly lower than those in the combined therapy group (P <0.05). The incidence of cardiovascular events in the three groups was 52.6%, 41.0%, and 38.5%, respectively, with no statistically significant differences (P=0.412). Logistic regression analysis indicated a weak correlation between iPTH levels and cardiovascular events (OR=1.002, 95% CI: 1.000-1.004, P=0.045). Conclusion Cinacalcet demonstrates superior efficacy in controlling iPTH levels in SHPT patients, and helps maintain lower serum calcium and phosphorus levels. Paricalcitol is suitable for long-term maintenance therapy. The combined therapy regimen needs further optimization to balance therapeutic effects and the risk of complications. This study provides a scientific reference for the SHPT drug combination strategy in hemodialysis patients.