San Antonio, Texas, was one of the first metropolitan areas where 2009 pandemic influenza A (H1N1) virus (pH1N1) was detected. Identification of laboratory-confirmed pH1N1 in 2 students led to a preemptive 8-day closure of their high school. We assessed transmission of pH1N1 and changes in adoption of nonpharmaceutical interventions (NPIs) within households of students attending the affected school. Household secondary attack rates were 3.7% overall and 9.1% among those 0-4 years of age. Widespread adoption of NPIs was reported among household members. Respondents who viewed pH1N1 as very serious were more likely to adopt certain NPIs than were respondents who viewed pH1N1 as not very serious. NPIs may complement influenza vaccine prevention programs or be the only line of defense when pandemic vaccine is unavailable. The 2009 pandemic provided a unique opportunity to study NPIs, and these real-world experiences provide much-needed data to inform pandemic response policy.