Studies about the relationship between antibiotic consumption and carriage of antibiotic-resistant Escherichia coli in individual patients have yielded conflicting results. The goal of this study was to identify individual- and household-level factors associated with carriage of ampicillin (AMP)-resistant E. coli during consumption of a course of oral antibiotics. We enrolled outpatients and their families in a prospective household study of AMP-resistant or AMP-susceptible E. coli carriage. Two kinds of index patients were identified. Group 1 consisted of outpatients who were being initiated on a new antibiotic course at the time of a clinic visit, and group 2 consisted of outpatients not starting antibiotics. Each participant was asked to submit three stool swab samples (at baseline, week 1, and week 4) and to complete a questionnaire. Antimicrobial susceptibility testing was performed on each phenotypically distinct E. coli colony. The study included 149 group 1 households (total, 570 participants) and 38 group 2 households (total, 131 participants). AMP-resistant E. coli was recovered from 29% of stool samples. Observed associations with antibiotic exposure varied by drug class. Penicillins, which were the most frequently prescribed drug class, were associated with a modest increase in AMP-resistant E. coli carriage and a modest decrease in AMP-susceptible E. coli carriage. Neither change by itself was statistically significant. Macrolides were associated with reduced carriage of both AMP-resistant E. coli and AMP-susceptible E. coli (P < 0.05). Both AMP-resistant and AMP-susceptible E. coli demonstrated household clustering (P < 0.001). In summary, the overall effect of antibiotics on individual risk of carriage of AMP-resistant E. coli was small. However, even a modest alteration of the competitive balance between AMP-resistant and AMP-susceptible E. coli may promote population spread of resistant E. coli. Examining changes in both resistant and susceptible organisms in antibiotic-treated individuals and their close contacts improves understanding of antibiotic selection pressure.