Background and Objectives: Chronic obstructive pulmonary disease (COPD) represents a debilitating disease, with rising morbidity and mortality. Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, vascular permeability, and airway remodeling. The purpose of this study was to investigate the relationship between VEGF serum levels and VEGF +936 C/T gene polymorphism (rs3025039) with COPD, for the first time in a Romanian population. Materials and Methods: In total, 120 participants from Transylvania were included in this case-control study. Serum levels of VEGF were determined using an enzyme-linked immune-sorbent assay and rs3025039 was investigated by high molecular weight genomic deoxyribonucleic acid (DNA). Spirometric values, arterial blood gas analysis, and the Six Minute Walk Test (6MWT) outcome were also determined. Results: The serum level of VEGF was higher in the COPD group versus controls (p p = 0.92, OR = 1.04, 95%CI = 0.41–2.62), but the presence of the T allele was significantly linked to the presence of COPD (chi2 test p = 0.02, OR = 2.36, 95%CI = 1.12–4.97). Conclusions: Higher VEGF serum levels were found in moderate and severe COPD and were positively correlated with the distance in the 6MWT. No significant difference was found between CC, CT, and TT genotypes of rs3025039 and the presence of COPD. The presence of the T allele was found to be linked to COPD and also to the degree of airway obstruction.