A system for priming an extracorporeal blood circuit is described. The system includes a fluid circuit (200) with an air venting mechanism, a reversible pump (222), arterial and venous lines, a prime waste bag (285) and a switchable coupler (220) selectively connecting the arterial and venous lines to the waste bag or alternatively interconnecting the arterial and venous lines. A priming fluid is connected to the circuit and circulated in the circuit under different configurations of the arterial and venous line connections.