<b><i>Background:</i></b> In the last decade, the proportion of people with asthma in the USA grew by nearly 15%, with 479,300 hospitalizations and 1.9 million emergency department visits in 2009 alone. The primary objective of our study was to evaluate in-hospital outcomes in patients admitted with asthma exacerbation in terms of mortality, length of stay (LOS) and hospitalization costs. <b><i>Methods:</i></b> We queried the HCUP's Nationwide Inpatient Sample (NIS) between 2001 and 2010 using the ICD9-CM diagnosis code 493 for asthma (n = 760,418 patients). The NIS represents 20% of all hospitals in the USA. Multivariate logistic regression analysis was used to evaluate predictors of in-hospital mortality. LOS and hospitalization costs were also analyzed. <b><i>Results:</i></b> The overall LOS was 3.9 days and as high as 8.3 days in patients requiring mechanical ventilation. LOS has decreased in recent years, though it continues to be higher than in 2001. The hospitalization cost increased steadily over the study period. The overall in-hospital mortality was 1% and as high as 9.8% in patients requiring mechanical ventilation. Multivariate predictors of longer LOS, higher hospitalization costs and in-hospital mortality included increasing age and hospitalizations during the winter months. Private insurance was predictive of lower hospitalization costs and LOS as well as lower in-hospital mortality. <b><i>Conclusion:</i></b> Asthma continues to account for significant in-hospital mortality and resource utilization, especially in mechanically ventilated patients. Age, admissions during winter months and the type of insurance are independent predictors of in-hospital outcomes.