Objective To determine the influence of a dual tourniquet technique and limb exsanguination on amikacin concentrations in the synovial fluid of the radiocarpal joint (RCJ) and distal interphalangeal joint (DIPJ) after low volume, cephalic intravenous regional limb perfusion (IVRLP). Study design Randomized cross‐over design. Animals Six healthy adult horses. Methods One gram of amikacin in 6 mL of 0.9% NaCl was infused via cephalic IVRLP in 6 standing, sedated horses using 4 techniques: proximal pneumatic tourniquet (P), proximal pneumatic tourniquet with exsanguination (PE), proximal pneumatic and distal Esmarch tourniquet (PD), and proximal pneumatic with distal Esmarch tourniquet and exsanguination (PDE). Amikacin concentrations were measured in RCJ and DIPJ synovial fluid samples, collected just before perfusion (time 0), and at 15 and 30 minutes (before tourniquet release) after perfusion. Results Synovial fluid amikacin concentrations achieved in the RCJ were higher with techniques PD and PDE than those achieved with techniques P and PE 15 and 30 minutes after perfusion (P < .0001). Synovial fluid amikacin concentrations in the DIPJ were higher with techniques P and PE than those achieved with techniques PD and PDE at 15 minutes (P = .0002) and were higher than technique PDE at 30 minutes after perfusion (P < .0001). Conclusion Low volume (10 mL) cephalic IVRLP should be combined with the placement of 2 tourniquets (proximal and distal to the carpus) to achieve therapeutic amikacin concentrations in the RCJ. Exsanguination prior to low volume IVRLP does not alter synovial fluid amikacin concentrations.