OBJECTIVE: To study the impact of preconception Chlamydia trachomatis seropositivity on fecundability, live birth, and pregnancy loss and to assess the effect of low-dose aspirin therapy (81 mg/day) on live birth and pregnancy loss. DESIGN: Preconception cohort study conducted using data and specimens from the Effects of Aspirin in Gestation and Reproduction study-a randomized placebo-controlled trial. SUBJECTS: A total of 1,228 individuals with proven fecundity and a history of 1-2 pregnancy losses. EXPOSURE: Preconception C. trachomatis seropositivity determined using an enzyme-linked immunoabsorbent assay-based synthetic peptide assay at baseline. MAIN OUTCOME MEASURES: Time-to pregnancy (fecundability) was defined as number of menstrual cycles to beta human chorionic gonadrotropin-detected pregnancy; live birth status was determined from medical record abstraction; pregnancy loss was defined as any loss post positive beta human chorionic gonadrotropin test. RESULTS: After adjusting for confounders (baseline demographic and reproductive history variables), C. trachomatis seropositivity (n = 134/1228, 11%) was associated with a reduced live birth likelihood (relative risk [RR]: 0.77, 95% confidence interval [CI]: 0.59, 0.99) and an increased risk of pregnancy loss (RR: 1.16, 95% CI: 1.04, 1.29), but was not associated with fecundability (fecundability odds ratio: 0.92, 95% CI: 0.71, 1.20). Among a subset of C. trachomatis seropositive individuals with chronic inflammation indicated by increased C-reactive protein levels ≥1.95 but ≤10 mg/L (n = 50/134, 37.3%), low-dose aspirin therapy improved live birth rates (RR: 1.68, 95% CI: 0.96, 2.92) and reduced the risk of pregnancy loss (RR: 0.83, 95% CI: 0.65, 1.10). However, the sample size reduced precision. CONCLUSION: Prior exposure to C. trachomatis among women with a history of pregnancy loss may impact risk of pregnancy loss. Our results indicate the need for future studies exploring mechanisms by which C. trachomatis may influence long-term reproductive function, because this may identify treatments to improve outcomes among those with a history of infection.