Introduction: Administration of UNFRACTIONATEDHEPARIN (UFH) is associated with rising of serum potassium, particularly in patients with renal failure.As an anticoagulant during hemodialysis, it is not yet clear whether Low Molecular Weight HEPARIN (LMWH) could reduce the risk of hyperkalemia in chronic hemodialysis patients.Methods: We performed a randomized case-control study at Shahid Faghihi hemodialysis center. A total of 40 patients with at least 6 months duration on hemodialysis were selected and were randomized to case and control groups with 20 patients in each group. The case group received UFH 5000 unit intravenously (IV) and control group Enoxaparin 40 milligram IV, both as single bolus without any additional dosages, for intradialytic anticoagulation.Serum levels of potassium, BUN, and phosphate were measured at the beginning and after 4 weeks.Results: As rough indices of nutritional status and hemodialysis efficacy, there was no significant difference between two groups in terms of BUN and phosphate level, at the beginning and the end of the study. Of those receiving UFH and LMWH, 6 (30%) and 7 (35%) had diabetes mellitus, respectively (P=.500).The serum level of potassium decreased significantly after 4 weeks of Enoxaparin (4.5 ± 0.5 versus 4.3 ± 0.4, P=.001) while it remained unchanged in those receiving UFH (4.6 ± 0.6 versus 4.6 ± 0.5, P=.486). The reduction of serum potassium was also significant in diabetic patients receiving Enoxaparin (4.8 ± 0.5 versus 4.6 ± 0.6, P=.006), but not in UFH group with diabetes (4.8 ± 0.6 versus 4.7 ± 0.6, P=.876).Conclusions: For anticoagulation during hemodialysis, replacing UFH by LMWH can reduce serum potassium level in chronic hemodialysis patients.