BACKGROUND: Therapeutic plasma exchange (TPE) is an important blood purification technology and most patients require multiple consecutive TPEs. Regional citrate anticoagulation (RCA) could be used for membrane therapeutic plasma exchange (mTPE). However, there is no research on the metabolic complications of the RCA for patients receiving multiple consecutive mTPEs with fresh frozen plasma (FFP) as a replacement solution. METHODS: We retrospectively included patients who used RCA for multiple consecutive mTPEs with FFP as a replacement solution in Xijing Hospital from 2020 to 2022. We collected blood gas analysis and electrolyte results before and after mTPE treatment and analysed the anticoagulation effectiveness and metabolic complications of the RCA. RESULTS: A total of 33 patients who underwent 131 mTPE sessions were included, and 129 (98.5%) sessions were successfully completed. Severe hypocalcemia (19.1%) and metabolic alkalosis (58.5%) were frequently observed. In single mTPE sessions, there was a significant decrease in ionized calcium levels and significant increases in serum sodium, potassium, pH, bicarbonate, and base excess (BE) levels compared to pretreatment values. When comparing the values after the last treatment to the baseline values in all 33 patients, the serum sodium, pH, bicarbonate, and BE levels increased significantly, while the ionized calcium decreased significantly. The levels of pH, bicarbonate, and BE increased with the number of mTPE sessions, and the cumulative incidence of metabolic alkalosis reached 95.2% after the fifth treatment according to the Kaplan-Meier survival analysis. CONCLUSION: RCA is an effective anticoagulation method for patients undergoing mTPE with FFP as a replacement solution. However, the metabolic complications associated with RCA, especially hypocalcemia and metabolic alkalosis, frequently develop in patients who undergo multiple consecutive mTPEs with FFP.