Magnesium salts alone or mixed with other minerals and vitamins are commonly used as dietary supplements. Also, magnesium is infused intra-operatively in a variety of surgeries. Magnesium is one of the most plentiful intracellular divalent cation and is a cofactor in approximately 300 enzymatic reactions. Magnesium is considered safe; however, there are some reports on its health risk when overdosed. It has been reported that Mg²⁺ ions play a role in blood clotting competing with Ca²⁺ ions. Moreover, magnesium has a different and conflicting role on proteins of coagulation cascade and its net action on coagulation is difficult to predict. For this reason we have investigated whether magnesium can change clotting characteristics of plasma and blood. We have found that magnesium increases the clotting time in plasma and in whole blood in a concentration-dependent fashion. Also, blood clotted in the presence of increased concentration of magnesium, has progressively shortened the lysis time of whole blood clots. We postulated that Mg²⁺ exerts its anticoagulant influence by acting at the stage of prothrombin activation in the blood coagulation cascade competing with calcium needed for thrombin activation. Shortening lysis of whole blood clots can utilize an alternative mechanism. PAI-1 in the presence of thrombin, vitronectin and Ca²⁺ or Mg²⁺ is inhibited, causing larger amounts of tPA to remain in the free form. Excessive amounts of tPA activate plasminogen that lyses clots faster. However, further investigations are required to determine the clinical relevance of these observations.