We retrospectively assessed the effectiveness of azithromycin in preventing transmission of pertussis to a patient's household contacts. We also considered the duration between symptom onset in the primary patient and azithromycin administration. We categorized contacts into 4 groups: those treated within <7 days, 8-14 days, 15-21 days, and >21 days after illness onset in the primary patient. We studied 476 primary index patients and their 1,975 household contacts, of whom 4.5% were later identified as having pertussis. When contacts started chemoprophylaxis within <21 days after the primary patient's symptom onset, the treatment was 43.9% effective. Chemoprophylaxis started >14 days after primary patient's symptom onset was less effective. We recommend that contacts of persons with pertussis begin chemoprophylaxis within <14 days after primary patient's symptom onset.