We compared the efficacy of a screening program for urogenital Chlamydia trachomatis infections based on home sampling with that of a screening program based on conventional swab sampling performed at a physician's office. Female subjects, comprising students at 17 high schools in the county of Aarhus, Denmark, were divided into a study group (tested by home sampling) and a control group (tested in a physician's office). We assessed the number of new infections and the number of subjects who reported being treated for pelvic inflammatory disease (PID) at 1 year of follow-up; 443 (51.1%) of 867 women in the intervention group and 487 (58.5%) of 833 women in the control group were available for follow-up. Thirteen (2.9%) and 32 (6.6%) new infections were identified in the intervention group and the control group, respectively (Wilcoxon exact value, P=.026). Nine (2.1%) women in the intervention group and 20 (4.2%) in the control group reported being treated for PID (P=.045), indicating that a screening strategy involving home sampling is associated with a lower prevalence of C. trachomatis and a lower proportion of reported cases of PID.