Background: Exacerbation of chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality, but the effect of metabolic compensation of respiratory acidosis (RA) on mortality is not fully understood. Objective: To investigate the relationship between metabolic compensation and mortality in COPD patients with RA. Methods: We prospectively investigated all COPD patients with RA admitted to the respiratory intensive care unit between February 2001 and March 2007. Two hundred and thirteen patients (159 male, 54 female; mean age 65 ± 10.8 years) were divided into three groups (71 patients each) according to base excess (BE) levels: (1) low BE, (2) medium BE, and (3) high BE. H+ concentration was calculated according to their standard formula and BE was calculated according to the Van Slyke equation. Results: The overall mortality rate was 24.9%. The group mortality rates were 32, 17 and 25% in the low, medium and high BE groups, respectively (p = 0.001). When patients were divided into three groups according to the HCO3– levels, the group mortality rate was 59.1% in the low HCO3– group and 19.8% in the high HCO3– group. Based on univariate analysis, six factors affecting mortality were identified. However, multivariate analysis showed that the levels of serum HCO3– (p = 0.013; OR: 0.552; CI: 0.345–0.882) and creatinine (p = 0.019; OR: 2.114; CI: 1.132–3.949) had an independent effect. Conclusion: In patients with COPD exacerbation and hypercapnia, the development of sufficient metabolic compensation and adequate renal function significantly decreases mortality.