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Large-scale strategies are needed to reduce overuse of antibiotics in US communities.To evaluate the impact of a mass media campaign—“Get Smart Colorado”—on public exposure to campaign, antibiotic use, and office visit rates.Nonrandomized controlled trial.Two metropolitan communities in Colorado, United States.The general public, managed care enrollees, and physicians residing in the mass media (2.2 million persons) and comparison (0.53 million persons) communities.The campaign consisting of paid outdoor advertising, earned media and physician advocacy ran between November 2002 and February 2003.Antibiotics dispensed per 1000 persons or managed care enrollees, and the proportion of office visits receiving antibiotics measured during 10 to 12 months before and after the campaign.After the mass media campaign, there was a 3.8% net decrease in retail pharmacy antibiotic dispenses per 1000 persons (P = 0.30) and an 8.8% net decrease in managed care-associated antibiotic dispenses per 1000 members (P = 0.03) in the mass media community. Most of the decline occurred among pediatric members, and corresponded with a decline in pediatric office visit rates. There was no change in the office visit prescription rates among pediatric or adult managed care members, nor in visit rates for complications of acute respiratory tract infections.A low-cost mass media campaign was associated with a reduction in antibiotic use in the community, and seems to be mediated through decreases in office visits rates among children. The campaign seems to be cost-saving.