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We describe school-based screening events in four Detroit, Michigan public high schools. To examine trends, we analyzed Chlamydia trachomatis data from 2010 to 2015. Prevalence of C. trachomatis decreased significantly (P < .01): from 10.24% to 6.27%. Future school-based screening events may bring about similar results if the program is instituted in a high-prevalence area and can achieve high student participation.