Background: There are no prior studies that assess the non-in vitro fertilization (IVF) pregnancy rates in chlamydia serology-positive versus serology-negative women. Therefore, we wanted to determine whether a positive Chlamydia trachomatis immunoglobulin G serology result predicts reduced clinical pregnancy rates without IVF. Methods: A prospective observational study was performed at a university-affiliated reproductive center. A total of 1279 new infertility patients seen at the Continuum Reproductive Center between January 2007 and June 2009 underwent C. trachomatis immunoglobulin G screening. Charts were later reviewed for hysterosalpingography, laparoscopy, treatment cycles, and ultrasound evidence of an intrauterine pregnancy. The main outcome measure was non-IVF cumulative pregnancy rates. Results: Seventy (5.5%) of 1279 of the participants were found to have a positive chlamydia serology result. Serology-positive participants had significantly more tubal block on hysterosalpingography (37.5% vs. 10.1%, P = 0.001) and laparoscopically confirmed tubal damage (85.7% vs. 48.9%, P = 0.002). The percent of all participants who achieved an ultrasound documented clinical pregnancy, at our center, without IVF was significantly lower among Chlamydia-positive participants (10.0% versus 21.7%) in seronegative participants (P < 0.02). The hazard rate of non-IVF clinical pregnancy among chlamydia antibody testing-positive patients was 57% less than the rate of pregnancy among chlamydia antibody testing-negative patients (hazard ratio, 0.43; 95% confidence interval, 0.20-0.92). Both the per-cycle and the cumulative IVF pregnancy rates were equivalent in seropositive and in seronegative participants. Conclusions: This is the first large study to report that a positive serology screening result is both predictive of tubal damage and a reduced cumulative pregnancy rate when excluding treatment with IVF.