Background: Controversy exists around the incidence and cause of hyperlactatemia during asthma exacerbations. We evaluated the incidence, potential causes, and adverse events of hyperlactatemia in patients with acute asthma exacerbation. Methods: This study was a subanalysis of subjects receiving placebo from a prospective, randomized trial evaluating an IV β-adrenergic agonist in acute asthma exacerbation. Plasma albuterol, serum lactate, and bicarbonate concentrations were measured at baseline and 1.25 h, and dyspnea score and spirometry were measured at baseline and hourly for 3 h. All subjects had a therapeutic trial comprising 5 to 15 mg nebulized albuterol, 0.5 to 1 mg nebulized ipratropium, and at least 50 mg oral prednisone or its equivalent prior to initiation of the study. Following randomization, subjects were treated with continued albuterol and IV magnesium at the discretion of their treating physician. Subjects were followed to hospital admission or discharge with follow-up at 24 h and 1 week. Results: One hundred seventy-five subjects were enrolled in the parent trial, with 84 in the placebo group. Sixty-five had complete data. Mean ± SD albuterol administration prior to baseline was 12.3 ± 5.3 mg. Mean baseline lactate was 18.5 ± 8.4 mg/dL vs 26.5 ± 11.8 mg/dL at 1.25 h (P < .001). Forty-five subjects (69.2%) had hyperlactatemia. Mean baseline bicarbonate level was 22.6 ± 2.9 mEq/L vs 21.9 ± 4.0 mEq/L at 1.25 h (P = .11). Plasma albuterol concentration correlated with lactate concentration (b = 0.45, P < .001) and maintained a significant association after adjusting for asthma severity (b = 0.41, P = .001). Hyperlactatemia did not increase the risk of hospitalization or relapse (P = .26) or was associated with lower FEV1 % predicted at 3 h (P = .54). Conclusions: Plasma albuterol was significantly correlated with serum lactate concentration after adjusting for asthma severity. Hyperlactatemia was not associated with poorer pulmonary function as measured by 3-h FEV1 % predicted or increased hospitalization or relapse at 1 week.