Objective To study the influence of calcium acetate tablets combined with compound alpha-keto acid on calcium and phosphorus metabolism in maintenance hemodialysis (MHD) patients. Methods A total of 112 MHD patients with hyperphosphatemia treated between May 2014 and May 2015 were included in this study. Based on random number table method, they were divided into calcium acetate group (n=37), compound alpha-keto acid group (n=36) and combined drug use group (n=39). All the patients were given a low protein diet. Twelve weeks after treatment, we compared the calcium and phosphorus metabolic indexes, nutrition indicator levels and adverse reactions within and across the three groups. Results Before treatment, there was no significant difference among the three groups in terms of serum calcium, phosphorus, calcium-phosphorus product, and parathyroid hormone (PTH) level (P>0.05). After treatment, the combined drug use group had significantly lower levels of serum phosphorus, calcium-phosphorus product and PTH than the other two groups (P<0.05). Before treatment, the levels of creatinine, serum total protein and albumin were not significantly different among the three groups (P>0.05). After treatment, the serum total protein and albumin level in the combined drug use group were significantly higher than those in the other two groups (P<0.01). Three was no significant difference among the three groups in terms of adverse reactions (P>0.05). Conclusions For MHD patients with hyperphosphatemia, the combined use of calcium acetate tablets and compound alpha-keto acid is better than the use of single drugs, which can effectively improve patients’ symptoms and reduce the level of serum phosphorus with high security. It is worthy of clinical recommendation.