Medical opinion varies considerably regarding the transmission of hepatitis C virus (HCV) through sexual contact. Based on the study design, representativeness of the study population, and the methods used for case ascertainment, we analyzed 80 qualifying reports regarding the evidence for or against sexual transmission. Regarding heterosexual transmission, the weight of evidence is that there is no increased risk of sexual transmission of HCV among heterosexual couples in regular relationships. This risk increases among persons with multiple sexual partners (adjusted odds ratio [aOR] 2.2-2.9), but this association may be confounded by increased likelihood of injection drug use with increased number of partners. There appears to be a real increased risk for women coinfected with human immunodeficiency virus (HIV) or other sexually transmitted infections (aOR 3.3-3.9) and especially for HIV-infected gay men who are having sex with one another compared with HIV-uninfected men (aOR 4.1-5.7). HIV-infected gay men increase their risk of such transmission in association with practices that lead to mucosal trauma (multiple sexual partners, fisting, use of sex toys) and the presence of genital ulcerative disease. Conclusion: This review should inform, and not distract from, recommendations to reduce the risk of HCV transmission. Health care providers need to pay special attention to sexual transmission of HCV among HIV-infected individuals. (HEPATOLOGY 2010;52:1497-1505) H epatitis C virus (HCV) infection is a bloodborne infection transmitted mainly through injection drug use (IDU), blood transfusions, organ transplantations, accidental needle sticks, 1,2 and other parenteral exposures, including inappropriate use or reuse of needles and syringes in health care settings. 3,4 Sexual transmission is a controversial mode of HCV transmission that has received considerable attention among health care providers and the lay public. For example, in 2009, the Centers for Disease Control and Prevention's Division of Viral Hepatitis received over 2,600 telephone and email inquiries about hepatitis C. When looking at available data that Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IDU, injection drug use; MSM, men who have sex with men; STI, sexually transmitted infection.