Posthypercapnic alkalosis (PHA) is frequently overlooked as a complication of mechanical ventilation in patients with exacerbation of chronic obstructive pulmonary disease (COPD). The current study was conducted to determine the incidence, risk factors for development and effect on outcome of PHA. Eighty-four patients (62 +/- 11 years, range 42-78 years, M:F 58: 26) with exacerbation of COPD with underlying chronic hypercapnic respiratory failure requiring mechanical ventilation were included in a retrospective fashion. PHA was defined as static or rising serum bicarbonate levels, 72 hours or more after return of PaCO2 to baseline, with concurrent pH > 7.44. Development of PHA was noted in 17 patients (20.2%). Corticosteroid use >or=10 days during the hospital stay was an independent risk factor for development of PHA (Adjusted OR, 95% CI: 9.4, 1.6-55.3; P = 0.013). Development of PHA was associated with an increased incidence of ventilator dependence (64.7% vs. 37.3%, OR, 95% CI: 3.1, 1.1-9.4, P = 0.04) and duration of ICU stay (14.7 +/- 6.7 vs. 9.5 +/- 5.9, P = 0.01) but no increase in hospital mortality (43.3% vs. 41.2%, P = NS). It is concluded that PHA is a common complication in patients with exacerbation of COPD requiring mechanical ventilation and is associated with increased incidence of ventilator dependence and ICU stay.