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Insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) and vascular endothelial growth factor-A (VEGF-A) may play important roles in the process of tumor progression and tumor angiogenesis. The aim of the present study was to examine the co-expression of IMP3 and VEGF-A in primary human non-small cell lung cancer (NSCLC), to investigate the association between these two expression levels and determine the clinicopathological implications, including changes to microvessel density (MVD), and to assess the prognostic value of co-expression. Using immunohistochemical staining, the expression of IMP3, VEGF-A and CD34 expression was detected in 128 primary NSCLC tissue samples. According to the expression of IMP3 and VEGF-A, the cases were divided into four groups. Next, the clinicopathological features, MVD and survival time were investigated across the different groups. The immunohistochemical analyses demonstrated that there was a significant correlation between IMP3 and VEGF-A expression in NSCLC (r=0.181; P=0.041). Co-expression of IMP3 and VEGF-A was significantly associated with larger primary tumor size (P=0.016), poorer differentiation (P=0.014), more advanced Tumor-Node-Metastasis stage (P=0.012), increased MVD (P=0.004) and positive lymph node metastasis (P=0.002). Survival analysis demonstrated that cases with IMP3 and VEGF-A double-positive staining were significantly associated with lower survival rates compared with cases with double-negative staining (P=0.039). In the early NSCLC (I–IIa) subgroup, the mean survival time of the double-positive staining group was significantly shorter compared with that of the double-negative staining group (P=0.015). Co-expression of IMP3 and VEGF-A was associated with angiogenesis and a poorer prognosis in NSCLC, and may therefore play a critical role in NSCLC progression. [ABSTRACT FROM AUTHOR]