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. Copyright (C) 2008 S. Karger AG, Basel.