The gastroepiploic artery (GEA) is a highly vasoactive artery gaining wider acceptance as a conduit for coronary artery bypass surgery. A variety of agents are used to dilate the GEA prior to grafting; however, little is known about the duration of their effect in the immediate postoperative period. This study evaluated three calcium channel blockers and papaverine in preventing graft spasm. Methods: Porcine GEA segments (10–12 cm in length) were connected to a computer-controlled perfusion system with a constant in-flow pressure and distal resistance to simulate bypass flow (80–100 ml/min). Norepinephrine (NE; 10 −9 to 10 −5 M) was given in incremental doses at baseline before the vasodilator, immediately after (0 hr), and again at 2 hr after the vasodilator. Changes in flow and ED 50 were recorded. Group INT (N= 25) received papaverine (PAP), diltiazem, nifedipine (NFP), or verapamil (VPL) intraluminally, while group EXT (N= 25) received the same dilators externally. Results: All arteries showed dose-dependent vasoconstriction to NE prior to treatment. Immediately after receiving the vasodilator, arteries in both groups (INT and EXT) showed initial protection against NE-induced spasm with the exception of arteries receiving NFD externally. However, at 2 hr, for group INT, only VPL and NFD prevented NE-induced graft spasm (VPL: 40.4 ± 6.8 ml/min vs 17.9 ± 3.3 ml/min and NFD: 27.0 ± 6.5 ml/min vs 13.1 ± 0.9 ml/min,P< 0.02). In group EXT, after 2 hr, only VPL- and PAP-treated grafts showed resistance to NE-induced vasospasm (VPL: 35.6 ± 7.3 ml/min vs 15.0 ± 6.9 ml/min and PAP: 47.4 ± 15.1 ml/min vs 8.0 ± 2.0 ml/min,P< 0.001). Conclusions: Papaverine, a lipophilic vasodilator, when given externally on the perivascular fat of the GEA, prevented graft spasm for up to 2 hr. In contrast, intraluminally applied papaverine did not show graft protection against NE-induced spasm. Nifedipine prevented NE-induced spasm only when given intraluminally. Verapamil proved to be the most potent and versatile vasodilator with effective graft protection of up to 2 hr whether applied externally or internally and was the preferred agent for protecting against GEA spasm.