Arterial blood gas (ABG) analysis has an important role in the clinical assessment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, arterial puncture or insertion of an arterial catheter has many drawbacks. The aim of this study was to evaluate whether venous blood gas (VBG) values of pH, partial pressure of carbon dioxide (PCO₂) and oxygen (PO₂), bicarbonate (HCO₃), and oxygen saturation (SO₂) can reliably predict ABG levels in patients with AECOPD. One hundred and thirty-two patients with a prior diagnosis of COPD presenting with acute exacerbation according to AECOPD criteria were included in this prospective study. AECOPD is defined as a recent increase in cough, wheezing, the volume and purulence of sputum or shortness of breath necessitating a change in regular medication, including corticosteroids or antibiotics. ABG samples were taken immediately after venous sampling, and both were analyzed. Linear regression analysis was performed and equations were established for the estimation of arterial values. The Pearson correlation coefficients for pH, PCO₂, HCO₃, PO₂, and SO₂ were 0.934, 0.908, 0.927, 0.252, and 0.296, respectively. There was a significant correlation between ABG and VBG values of pH, PCO₂, and HCO₃ (p < 0.001). Linear regression equations for the estimation of pH, PCO₂, and HCO₃ were as follows: arterial pH = 1.004 × venous pH; arterial PCO₂ = 0.873 × venous PCO₂; and arterial HCO₃ = 0.951 × venous HCO₃. VBG analysis can reliably predict the ABG values of pH, PCO₂ and HCO₃ in patients with AECOPD.