Background Balloon release pressure may increase the incidence of no reflow after direct percutaneous coronary intervention (PCI). This randomized controlled study was designed to analyze the correlation between balloon release pressure and no-reflow in patients with acute myocardial infarction (AMI) undergoing direct PCI. Methods There were 156 AMI patients who underwent PCI from January 1, 2010 to December 31, 2012, and were divided into two groups according to the stent inflation pressure: a conventional pressure group and a high pressure group. After PCI, angiography was conducted to assess the thrombolysis in myocardial infarction (TIMI) grade with related artery. Examinations were undertaken on all patients before and after the operation including cardiac enzymes, total cholesterol, low-density lipoprotein, blood glucose, homocysteine, beta-thromboglobulin (beta-TG), Hamilton depression scale (HAMD) and self-rating anxiety scale (SAS). After interventional therapy, the afore-mentioned parameters in both the conventional pressure group and high pressure group were again analyzed. Results The results showed that CK-MB, HAMD, SAS were significantly different (P <0.05) in all patients after PCI, especially the CK-MB in the high pressure group ((25.7 +/- 7.6) U/L vs. (76.7 +/- 11.8) U/L). CK-MB, HAMD, SAS, and beta-TG were comparative before PCI but they were significantly changed (P <0.05) after intervention. No-reflow phenomenon occurred in 13 patients in the high pressure group, which was significantly higher than in the conventional pressure group (17.11% vs. 6.25%, P <0.05). Conclusion In stent implantation, using a pressure less than 1823.4 kPa balloon to release pressure may be the better choice to reduce the occurrence of no-reflow following direct PCI.