OBJECTIVES: In patients undergoing chronic hemodialysis, unfractionated heparin (UFH) is widely used for prevention of extracorporeal circuit thrombosis.  Low-molecular-weight heparin (LMWH) may have advantages in terms of bleeding risk.  The objective of this study was to review the effectiveness, safety and cost-effectiveness of LMWH versus UFH in chronic hemodialysis to inform a hospital formulary policy decision. METHODS: A systematic review was conducted of randomized (RCTs) and non-randomized trials (non-RCTs) published to April 2010 evaluating the effectiveness, safety or cost-effectiveness of LMWHs for use in hemodialysis compared with UFH.  Outcomes included extracorporeal circuit thrombosis, bleeding events, vascular access compression time, heparin-induced thrombocytopenia, and cost-effectiveness. Where possible, data was pooled via a random-effects model. RESULTS: After reviewing 998 citations, 25 studies were included (1 systematic review, 12 RCTs, 12 non-RCTs).  Meta-analysis of RCTs demonstrated no statistically significant differences between LMWH and UFH for bleeding (relative risk (RR)=0.70, p=0.66) or compression time (weighted mean difference= -2.49, p=0.31).  Pooled RR for circuit thrombosis was 1.32 (p=0.05) and 0.67 (p=0.69) in studies assessing the number of dialysis session and patients, respectively.  Pooled results for the non-RCTs were not significantly different between LMWH and UFH.  No studies evaluating the cost-effectiveness of LMWH versus UFH were identified, however 4 cost analyses evaluated treatment costs.  Despite higher drug acquisition costs with LMWH, overall costs were lower or comparable when considering differences in nursing time associated with administration and monitoring. CONCLUSIONS: LMWH demonstrated no clear advantage over UFH in terms of effectiveness or safety, but may result in lower or comparable overall hospital costs.