Although asymptomatic bacteriuria during pregnancy is associated with an increased risk of developing pyelonephritis, the effectiveness of screening programs to reduce this risk is controversial. A sharp reduction in the annual incidence of pyelonephritis (1.8% to 0.6%, P < .001) occurred after the introduction of a program to screen and treat asymptomatic bacteriuria among pregnant women followed at a large teaching hospital. The data provide retrospective and prospective evidence that screening and treatment programs for asymptomatic bacteriuria during pregnancy reduce the risk of pyelonephritis in a population with a moderate to high prevalence of bacteriuria.