Introduction: Limited work has directly compared the role of different neighborhood factors or examined their interactive effects on pediatric asthma outcomes. Our objective was to quantify the main and interactive effects of neighborhood deprivation and residential instability (RI) on pediatric asthma outcomes. Methods: We conducted a retrospective cross-sectional study of patients with a primary diagnosis of asthma hospitalized at a tertiary care pediatric hospital. Residential addresses at the index hospitalization were linked to the state area deprivation index (ADI). RI was coded as the number of residences in the past 4 years. Logistic and ordinal regression and Cox regression survival analyses were used to estimate the effect on the primary outcomes of chronic asthma severity (intermittent, mild persistent, moderate persistent, severe persistent/other) as defined by the National Heart, Lung, and Blood Institute, severe hospitalization (requiring continuous albuterol or intensive care unit care), and time to emergency department (ED) readmission and rehospitalization within 365 days of the index visit, respectively. Results: In the sample (N = 664), 21% had severe persistent/other asthma, 22% had severe hospitalization, 37% were readmitted to the ED, and 19% were rehospitalized. Increasing RI was independently associated with more severe chronic asthma (odds ratio = 1.18, 95% confidence interval [CI] = 1.05, 1.32, P =.004), greater risk of 365-day ED readmission (hazard ratio [HR] = 1.10, 95% CI = 1.05, 1.15, P <.0001), and greater risk of 365-day rehospitalization (HR = 1.09, 95% CI = 1.03, 1.14, P =.002). There were no significant associations between ADI and these outcomes. Further, we did not find significant evidence of interactive effects. Conclusions: RI appears to be modestly associated with pediatric asthma outcomes, independent of current neighborhood deprivation.