Monitoring unfractionated heparin (UFH) using the activated partial thromboplastin time (APTT) or the anti-factor Xa (anti-Xa) chromogenic assay still seems to be a controversy. Is the anti-Xa less affected by pre-analytical variables in monitoring subjects on UFH and the low molecular weight heparins (LMWH)? Which assay is more accurate in monitoring heparin to achieve therapeutic levels, cost effective in time spent monitoring patients, use of blood products, time in the hospital, and overall cost which may include laboratory testing time. The APTT still is the most commonly used assay to monitor UFH therapy but cannot be used to monitor the LMWHs. Previous studies have cited interference in monitoring UFH with the APTT from oral anticoagulants, oral contraceptives, lupus anticoagulants, factor deficiencies, elevated acute phase reactants (fibrinogen, FVIII), low anti-thrombin, the APTT reagent sensitivity and instrumentation. The anti-Xa assay may be affected by hyperbilirubinemia, hyperlipidemia (can be cleared by ultracentrifugation) and decreased anti-thrombin levels (assay dependent). The anti-Xa assay can be used to monitor all heparin analogues and direct oral anticoagulants (DOACs). This presentation will discuss the pros and cons of both methods and which may be most effective in patient care.