Background: Sexually transmitted disease (STD) clinic attendees are considered to be at higher risk of sexually transmitted infections (STIs) than the general population. However, little is known about STD clinic subpopulations and their unique risks for STI's. The goal of this project was to begin to characterize an important STD clinic subpopulation, the small proportion of women reporting a recent history of multiple sex partners. Methods: Screening of electronic medical records from 2007 identified 347 (7%) women with 4 partners in the last 12 months. Records for women with 4 sex partners were matched with women reporting 1 sex partner in the last 12 months. Demographic, sexual history, STI history, and laboratory diagnosis(es) were extracted from the electronic medical record and compared using a case-control study design. Results: Approximately 5000 women presented to our STD clinic in 2007; 7.0% reported 4 sex partners. Women with 4 sex partners were less often black and on average younger than women with single partners (Median age, 24 vs. 29). They reported more nonvaginal sex, more same-sex contacts, but more consistent condom use than women with single partners. Dyspareunia, genital lesions, abdominal pain, and skin findings were more commonly reported by women with 4 sex partners. Women with multiple partners were also more likely to report ever having had 3 STI's and were more likely to report a history of gonorrhea or syphilis. They were also more likely to be diagnosed at presentation with chlamydia, gonorrhea, or syphilis. Conclusion: Women reporting multiple sex partners are an important minority among STD clinic attendees. Understanding the antecedents to high risk sexual behavior as determined by partner number is an important step in reducing STI's in this group. Copyright © 2011 American Sexually Transmitted Diseases Association All rights reserved.