Background: The natural history of Neisseria gonorrhoeae (GC) infections is largely unknown. The objective of the current study was to use sequential weekly vaginal samples and molecular techniques to describe the natural history of incident gonorrhea infections in adolescent women. Methods: A cohort of 387 adolescent women aged 14 to 17 were enrolled from urban, primary care clinics and followed longitudinally for a period of up to 8 years. Weekly vaginal swabs and daily diaries were provided during 12-week periods biannually, beginning and ending with a clinic visit, where all identified infections were treated. For this study, specimens and data from 16 women who became infected with GC during a weekly sampling period were analyzed. Results: GC organism load was highly variable between subjects. The number of organisms did not significantly differ across the first 6 weeks of infection (P = 0.59). Organism load did not differ among women with a previously documented GC infection at week 1 (P = 0.43) or across the first 6 weeks of infection (P = 0.67). The association of concurrent chlamydial infection on gonorrhea organism load was borderline significant over the first 6 weeks of infection (P = 0.06). Conclusions: Individual shedding patterns varied widely, and GC organism load did not decline in women for at least several weeks and were not associated with genitourinary symptoms. Chlamydia coinfection is associated with higher GC organism loads, potentially increasing chances of transmission. This study utilized a standardized quantification technique to assess GC organism load. © 2011 American Sexually Transmitted Diseases.