IMPORTANCE: The World Health Organization recommends at least 3 annual mass drug administrations (MDAs) of azithromycin in places where the prevalence of follicular trachoma (FT) is greater than 10%. However, stopping MDA prior to 3 rounds, if monitoring indicates an absence of infection with Chlamydia trachomatis even if FT persists, may be more cost-effective. OBJECTIVE: To determine the prevalence of infection in communities randomized to 3 rounds of annual MDAs with azithromycin compared with communities randomized to a stopping rule, where MDA could cease if the infection rate was low. DESIGN A 1:1 community randomized trial comparing usual care with a cessation rule. The Partnership for the Rapid Elimination of Trachoma-Ziada Trial was conducted from February 1, 2010, through September 1, 2011. SETTING: Sixteen communities in Tanzania with trachoma prevalence rates between 10% and 20%. PARTICIPANTS: A total of 100 children aged 5 years or younger randomly drawn from each community. Children had to reside in an eligible community, have no ocular condition that prevented trachoma grading or ocular specimen collection, and have a guardian who could provide consent for participation. INTERVENTIONS: Cessation of MDA with azithromycin if the community had no infection in their sample at 6 months or 18 months. MAIN OUTCOME MEASURE: The prevalence of C trachomatis at 18 months. RESULTS: None of the intervention communities met criteria to stop MDA based on the 6-month or 18-month survey; all, as well as the usual care communities, were scheduled for a third MDA round. There was no difference in infection (2.9% vs 4.7%; P = .25) between the usual care and cessation rule communities at 18 months. CONCLUSIONS AND RELEVANCE: In this setting, communities with low (10%-20%) initial prevalence of active trachoma did not have MDA stopped before 3 annual rounds on the basis of monitoring for infection. Infection with C trachomatis in communities with average trachoma rates at 12% to 13% cannot be eliminated before 3 rounds of MDA with azithromycin. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00792922.