In this study, the relaxatory effect of DETA-NONOate is compared with that of papaverine on isolated human internal mammary artery. We investigated the inhibitory effects of DETA-NONOate and papaverine on phenylephrine-induced contractile response in internal mammary artery segments. The internal mammary artery segments, taken from methodologically matched patients who underwent coronary artery bypass grafting, were prepared, placed in an organ bath, and contracted with phenylephrine (10(-9) to 10(-4) mol/L) to investigate their relaxatory response to DETA-NONOate or papaverine. Phenylephrine dose-response contraction was obtained after 1, 2, and 3 h in segments pre-incubated with DETA-NONOate or papaverine for 30 min. The EC50 that presented for internal mammary artery segments incubated with DETA-NONOate was 3.523 ± 1.2696 × 10(-7) mol/L, and for papaverine was 3.467 ± 1.2145 × 10(-6) mol/L. In segments pre-incubated with DETA-NONOate, the contractile response to phenylephrine was suppressed in the first 2 h post-incubation, compared with control responsive groups (p < 0.05), but this inhibition was revoked after 3 h post-incubation. We showed that DETA-NONOate has a more significant relaxative effect by comparison with papaverine; moreover, continuous and long-lasting nitric oxide production by DETA-NONOate might be of great importance for the outcome from coronary artery bypass grafting, when internal mammary artery is used as a conduit.