The majority of cardiovascular events in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PPCI) arise from the progression of nonculprit lesions (NCL) during the long-term follow-up period. However, the clinical and angiographic factors related to the progression of nonculprit lesions are unknown. The purpose of the study was to investigate the clinical and angiographic factors related to the progression of nonculprit lesions of patients with STEMI undergoing PPCI. A total of 492 patients with STEMI who underwent PPCI from January 2006 to December 2009 were enrolled. All patients underwent PPCI as a treatment for the culprit lesion. The clinical and angiographic follow-up was performed at 12 months. Primary endpoint: Clinically driven nonculprit lesion PCI. The levels of serum catecholamines [epinephrine (E), norepinephrine (NE)] and C-reactive protein (CRP) were assayed, and the clinical and angiographic features were also analyzed. The clinical and angiographic follow-up was performed in 492 patients, and 45 patients underwent clinically driven nonculprit lesions PCI (study group). A total of 447 patients were free of additional PCI (control group). There were significant differences in the level of catecholamines (E (621.48 +/- 79.31) pg/mL versus (268.14 +/- 73.26) pg/mL, P < 0.0001), NE (6212.43 +/- 822.41) pg/mL versus (3218.34 +/- 614.16) pg/mL, P < 0.0001), CRP (3.29 +/- 1.31) mg/dL versus (2.51 +/- 1.14) mg/dL, P < 0.0001, cTnI peak value (27.27 +/- 4.02) ng/mL versus (16.12 +/- 3.23) ng/mL, P < 0.0001), thrombotic lesion rate ((62.22% versus 23.04%), P < 0.0001), 2 vessel lesions rate (80.00% versus 46.09%), P < 0.0001), culprit lesion length ((33.2 +/- 2.9 versus 28.1 +/- 3.1), P = 0.013), and complex lesion rate ((57.78% versus 36.02%), P = 0.006) between the two groups. Correlation analysis between nonculprit lesion stenosis degree and serum E, serum NE, serum CRP, cTnI peak value, thrombotic lesion rate, 2 vessel lesions rate, culprit lesion length, and complex lesion rate showed that there were significant correlations between serum E, serum NE, serum CRP, cTnI peak value, thrombotic lesion rate, >= 2 vessel lesions rate, culprit lesion length, complex lesion rate, and nonculprit lesion stenosis degree. The correlation coefficients were 0.95, 0.97, 0.83, 0.90, 0.81, 0.84, 0.95, and 0.96, respectively, and P < 0.0001, P < 0.0001, P = 0.01, P = 0.01, P = 0.01, P = 0.01, P < 0.0001, and P < 0.0001, respectively. Recurrent PCI was mainly due to nonculprit lesion progression in patients with STEMI after primary PCI. Complex nonculprit lesions may be prone to for additional PCI. Chronic inflammation and sustained stress may be involved in the progression of nonculprit lesions in patients with STEM.