Female sex workers in Nairobi were prospectively evaluated for risk factors of incident Chlamydia trachomatis infection. Independent risk factors included cervical ectopy (P = .007), gonococcal infection (P = .002), human immunodeficiency virus (HIV) seropositivity (P = .003), HIV seroconversion (P = .001), and duration of prostitution (P = .002). Eighteen different C. trachomatis outer membrane protein (omp1) genotypes were identified, with the allelic composition of the C. trachomatis population changing significantly over time (P = .005). Seventeen of 19 reinfections ⩾6 months apart were with different C. trachomatis ompi genotypes. Women with HIV infection had an increased proportion of visits with C. trachomatis infection (P = .001) and an increased risk of reinfection (P = .008). Overall, the data demonstrate significant fluctuations in the genotype composition of the C. trachomatis population and a reduced rate of same-genotype reinfection consistent with the occurrence of strain-specific immunity.