Although slow/no-reflow is a serious problem complicating primary percutaneous coronary interventions (PCI) for acute myocardial infarction (AMI) and is associated with a poor prognosis, its efficacious treatment remains problematic. We compared the acute, in-hospital and long-term (1 year) effects of nitroprusside (NTP) with those of nicorandil (NC) on the slow/no-reflow phenomenon. Forty-nine of 442 consecutive patients with AMI who underwent primary PCI complicated by slow/no-reflow and who received intracoronary NTP (n = 25) or NC (n = 24) administration were studied. Both NTP and NC induced significant improvements in coronary flow, with increases in TIMI flow grade from 1.64 ± 0.62 to 2.74 ± 0.36 (p < 0.001) and 1.60 ± 0.86 to 2.23 ± 0.91 (p < 0.001), and in corrected TIMI frame count from 37.8 ± 15.1 to 13.7 ± 7.1 (p < 0.001) and 30.8 ± 20.7 to 19.3 ± 17.9 (p < 0.001), respectively. The degree of improvement in TIMI flow grade (post–pre/pre) and TIMI frame count (pre–post/pre) showed that NTP was more effective than NC (NTP vs. NC: 0.88 ± 0.79, 0.37 ± 0.37, p = 0.008; 0.59 ± 0.23, 0.36 ± 0.27, p = 0.003, respectively). Congestive heart failure did not tend to last beyond 3 days after onset in the NTP group, which was more than in the NC group, during hospitalization (1/25, 4/24, p = 0.143, respectively). At the 1-year follow-up, the NTP group tended to show more improvement than the NC group in MACE (5/25, 9/24, p = 0.175, respectively). NTP is a more effective treatment for slow/no-reflow associated with PCI in patients with AMI and may improve long-term clinical outcomes compared with NC.