Case–Crossover Study of Partner and Situational Factors for Unprotected Sex *George R. Seage III, ‡Sarah Holte, §Michael Gross,  Beryl Koblin, ¶Michael Marmor, #Kenneth H. Mayer, and †William R. Lenderking *Harvard School of Public Health and †Harvard Medical School, Boston, Massachusetts; ‡Fred Hutchinson Cancer Research Center, Seattle, Washington; §Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland;  New York Blood Center, and ¶New York University School of Medicine, New York, New York; and #Memorial Hospital and Brown University, Providence, Rhode Island Objectives: To identify situational and partner characteristics associated with un- protected sex among women at risk for HIV infection. Methods: The most recent unprotected and protected sexual encounters were com- pared using a case–crossover design among 1,647 women enrolled in a prospective cohort study conducted in six U.S. cities. Information collected via audio computer– assisted self-interview included detailed situational and partner characteristics for par- ticipants’ most recent sexual encounters, with and without condom use. Paired odds ratios (ORs) and 95% confidence intervals were calculated for situational or partner characteristics that may differ between unprotected and protected sexual encounters, using conditional logistic regression. Results: In the adjusted analysis, partner age of older than 40 years (OR  2.42), partner type (OR  2.45 for a “steady” partner), partner use of alcohol (OR  1.67) and drugs within 2 hours (OR  1.42) of the sexual encounter, time since the encounters (OR  0.41, 0.33, and 0.19), and exchange of sex for money or drugs (OR  0.68) remained significantly associated with women’s most recent unprotected sexual encounter. Conclusions: Considerations related to partner and relationship characteristics should provide information for the development of interventions for women. Key Words: HIV risk behaviors—Case–crossover design—HIV epidemiologic methods. AIDS is the third leading cause of death in 25- to 44-year-old U.S. women, with the greatest increases in recent years in those with heterosexually transmitted cases (1–3). In a recent prospective cohort study of 865 women at risk for HIV infection, the incidence of HIV infection among female injection drug users (1.24 cases per 100 person-years) and noninjecting females (1.13 cases per 100 person-years) was severalfold higher than that among male injection drug users (0.38 case per 100 person-years) (4). For noninjecting females, it has been estimated that the risk of HIV transmission is 1 per 1,000 acts of unprotected vaginal intercourse (5). There have been numerous published studies identify- ing factors associated with unprotected vaginal inter- course. In most reports, investigators attempted to asso- ciate unprotected vaginal intercourse with general sociodemographic or psychologic characteristics, such as age, race/ethnicity, education, depression, substance use, or empowerment (6–25). These “global” studies corre- lated potential predictors of unsafe sex, such as overall substance use, with outcomes, such as unprotected sex, Address correspondence and reprint requests to Dr. George R. Seage III, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; e-mail: gseage@ hsph.harvard.edu Manuscript received May 14, 2001; accepted August 12, 2002. JAIDS Journal of Acquired Immune Deficiency Syndromes 31:432–439 © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia 432