Sexually transmitted infections (STIs) are infections that are primarily transmitted through sexual contact (e.g., vaginal, anal, or oral intercourse). The STIs with the most substantial public health impact in the United States include human immunodeficiency virus (HIV), hepatitis B virus infection (HBV), herpes simplex virus (HSV) 1 and 2, human papillomavirus (HPV), Chlamydia trachomatis, Neisseria gonorrhea, Treponema pallidum (syphilis), and Trichomonas vaginalis. Other STIs include bacterial vaginosis (BV), granuloma inguinale, chancroid, pubic lice, and Sarcoptes scabiei var. hominis (scabies). The Centers for Disease Control (CDC) estimate that approximately 20 million new cases of STIs occur each year in the United States and more than two thirds of those cases are among persons ages 15 to 24 years. Point prevalence for any of the five most common STIs among females ages 14 to 19 was 24 percent in 2003 to 2004, and 38 percent among those who were sexually active. In 2010, the inflation-adjusted annual direct medical costs of STIs (including HIV) were $16.9 billion in the United States. This systematic review addresses the benefits and harms of behavioral sexual risk reduction counseling interventions in primary care to prevent STIs among adolescents and adults. We developed an analytic framework and four key questions to guide our review: 1. Is there direct evidence that behavioral counseling interventions to reduce risky sexual behaviors and increase protective sexual behaviors reduce STI incidence and/or related morbidity and mortality? a. Are there populations or intervention characteristics that influence the effectiveness of the interventions? 2. Do behavioral counseling interventions to prevent STIs reduce risky sexual behavior or increase protective sexual behavior? a. Are there populations or intervention characteristics that influence the effectiveness of the interventions? 3. Are there other positive outcomes beside STI incidence and changes in risky or protective sexual behavior from behavioral counseling interventions to prevent STIs? 4. What adverse effects are associated with behavioral counseling interventions to prevent STIs in primary care?