Objective To evaluate the safety and efficacy of simplified regional citrate anticoagulation in sustained low efficiency dialysis (SLED). Methods We prospectively analyzed the patients with acute kidney injury or end stage renal disease in Department of Nephrology, West China Hospital of Sichuan University from March 2017 to May 2018. All the patients received SLED treatment by Fresenius 4008s ARrTplus through either femoral or internal jugular venous catheter, with each session of SLED treatment lasting for 8 to 10 hours. We pumped in 4% tri-sodium citrate solution through the arterial line at 300 mL/h and citrate infusion was stopped 15 minutes before ending of treatment. The blood flow was 150 mL/min while the calcium-containing dialysate (Ca 1.25 mmol/L) was delivered at 200 mL/min. We recorded peripheral, post filter ionized calcium level, and systemic citrate concentration at 0, 2 and 6 hours, respectively. Results Sixty-two patients underwent 185 sessions of SLED. Three sessions of two patients were discontinued for filter clotting, while the rest 182 SLED sessions (98.4%) were all successfully completed. The systemic citrate concentrations at 2 and 6 hours after beginning were of no statistical difference [(0.82±0.31) vs. (0.86±0.31) mmol/L, P=0.21]. The 0-, 2-, 6-hour peripheral blood ionized calcium levels were (1.12±0.21), (1.09±0.12), and (1.11±0.09) mmol/L, respectively, with no significant difference (P>0.05), and post filter ionized calcium at 2 and 6 hours after beginning were recorded as (0.35±0.06) and (0.31±0.04) mmol/L. The trans-membrane pressure at 2 and 6 hours after beginning were (106.2±13.8) and (105.3±22.4) mm Hg (1 mm Hg=0.133 kPa), with no significant difference (P=0.42). At 6 hours after beginning, prothrombin time and activated partial thrombin time were identified to be similar to those before SLED. During SLED treatments, in 4 sessions (2.2%), patients suffered mild metabolic alkalosis, but all of them recovered 4 hours later by themselves. No bleeding complication, thrombocytopenia, cardiac arrhythmia, hypernatremia, metabolic alkalosis or hypotension was observed. Conclusion SLED under simplified citrate anticoagulation is safe and effective by using calcium containing dialysate, which achieves satisfying regional anticoagulation effect without interfering systemic clotting function, and provides a new option of anticoagulation for SLED.