Purpose. We describe two recent cases of intraosseous (IO) access resulting in amputation in critically ill infants and make contemporary recommendations on the safe practice of this technique. Methods/results. This is a retrospective case series of two children transferred from peripheral hospitals to our unit. One child (5 months) was resuscitated after cardiorespiratory decompensation due to diaphragmatic hernia. The other child (18 months) deteriorated during presentation with purpura fulminans two days after a scald injury. Both children underwent emergent bilateral tibial IO access using power driven needle systems. Initial resuscitation included large volumes of 0.9% normal saline. One child received doses of adrenaline and 8.4% sodium bicarbonate, whole blood and an initial dopamine infusion; the other received 8.4% sodium bicarbonate, 10% calcium gluconate and whole blood. Total infused volumes were 400mL and 730 ml respectively. Progressive lower limb tension became evident in both children after 12 hours; bilateral posterior tibial fractures were noted in one child. Ultimately, both children underwent surgical fasciotomy, but extensive necrosis necessitated unilateral below knee amputation at days 12 and 13 respectively. Conclusions. Fluid extravasation has been implicated in complicating IO access, particularly with high volume or prolonged infusions. Other potentiating factors include inaccurate needle placement, needle dislodgement during transfer and repeated infusion of irritant solutions. All of these contributed to irreversible lower limb ischaemia in these two cases. Adherence to the principles of careful needle placement, splinting, limited length of infusion and repeated monitoring of the limb will help avoid this devastating complication