Pest infestation is a major problem in urban, low-income housing and may contribute to elevated asthma prevalence and exacerbation rates in such communities. However, there is poor understanding of the effectiveness of integrated pest management (IPM) efforts in controlling pediatric asthma, or of the interactions among various interventions and risk factors in these settings. As part of the Boston-based Healthy Public Housing Initiative, we conducted a longitudinal, single-cohort community-based participatory research intervention study. Fifty asthmatic children aged 4–17 from three public housing developments in Boston, Massachusetts, USA successfully completed interventions and detailed environmental, medical, social, and health outcome data collection. Interventions primarily consisted of IPM and related cleaning and educational efforts, but also included limited case management and support from trained community health advocates. In pre-post analyses, we found significant reductions in a 2-week recall respiratory symptom score (from 2.6 to 1.5 on an 8-point scale, p = 0.0002 ) and in the frequency of wheeze/cough, slowing down or stopping play, and waking at night. Longitudinal analyses of asthma-related quality of life similarly document significant improvements, with a suggestion of some improvements prior to environmental interventions with an increased rate of improvement subsequent to pest management activities. Analyses of potential explanatory factors demonstrated significant between-development differences in symptom improvements and suggested some potential contributions of allergen reductions, increased peak flow meter usage, and improved social support, but not medication changes. In spite of limitations with pre-post comparisons, our results are consistent with aggressive pest management and other allergen reduction efforts having a positive impact on clinical health outcomes associated with asthma. Our findings reinforce the multifactorial nature of urban asthma and suggest a need for further study of the relative contributions of and possible synergies between environmental and social factors in asthma intervention programs.