Preoperative anaemia and intraoperative blood loss result in ∼90% of individuals being anaemic following hip and knee arthroplasty. Reducing blood loss offers the opportunity to improve outcomes and reduce the risk of transfusion and costs. This review's aim was to determine the effectiveness of drugs for preventing blood loss, and identify optimal dose, route, and timing of administration. Cochrane network meta-analysis of randomised controlled trials was conducted. Inclusion criteria: adults undergoing primary or revision elective hip or knee arthroplasty. Drugs studied: tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid, desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants, and non-fibrin sealants. Primary outcomes: need for allogenic blood transfusion, all• cause mortality (within 30 days). Secondary outcomes: mean number of transfusion episodes, re-operation, length of hospital stay and adverse events (DVT, PE, CVA, MI). 102 studies with 8418 participants. Trials included more women (63%). 47 studies (4398 participants) were included within the blood transfusion NMA. TXA given intra-articularly and orally at a total dose of greater than 3g pre-incision, intraoperatively and postoperatively ranked the highest, with anticipated absolute effect of 147 fewer transfusions per 1000 (53% chance ranking 1st) (relative risk(RR) 0.02, 95% credible interval(CrI) 0–0.31); moderate-certainty). Aprotinin (RR 0.59, 95%:CrI 0.36–0.86; low certainty evidence), fibrin (RR 0.86, CrI 0.25–2.93; very-low certainty) and EACA (RR 0.60, 95%:CrI 0.29–1.27; very-low certainty) were not shown to be as effective as TXA. TXA was the most effective drug for preventing bleeding in lower limb arthroplasty. Aprotinin and EACA were not as effective. Currently, the optimal dose, route and timing of administration of TXA is unclear. However, TXA given at higher doses and via mixed routes ranked higher in the treatment hierarchy. Oral TXA may be as effective as intavenous. There was no evidence of harm associated with higher doses of TXA