San Diego, California shares the world's busiest land border crossing with Tijuana, Mexico-a city where 95 % of injection drug users (IDUs) test hepatitis C virus (HCV) antibody-positive. Yet, little is known about the prevalence and risk behaviors for HCVamong IDUs in San Diego. In 2009-2010 IDUs in San Diego County completed a risk assessment interview and serologic testing for HCV and HIV infection. Recruitment involved respondent-driven sampling, venue-based sampling at a syringe exchange program, and convenience sampling. Correlates of HCV infection were identified by multivariable logistic regression. Among 510 current IDUs, 26.9 % (95 % CI 23.0-30.7 %) and 4.2 % (95 % CI 2.4-5.9 %) had been infected with HCVand HIV, respectively. Overall, median age was 28 years; 74 % were male; 60 % white and 29 % Hispanic; and 96 % were born in the U.S. Median years of injecting was 6; 41 % injected daily; 60 % injected heroin most often; 49 % receptively shared syringes and 68 % shared other injection paraphernalia; and only 22 % reported always using new syringes in the past 3 months. Two thirds had ever traveled to Mexico and 19 % injected in Mexico. HCV infection was independently associated with sharing injection paraphernalia (adjusted odds ratio [AOR]= 1.69) and SEP use (AOR=2.17) in the previous 3 months, lifetime history of drug overdose (AOR=2.66), and increased years of injecting (AOR=2.82, all P values G0.05). Controlling for recruitment method did not alter results. HCV infection prevalence among IDUs in San Diego was modest compared to other US cities and much lower than Tijuana. Given that known individual-level HCV risk factors were common in San Diego, the city's lower HCV prevalence might be due to differences in social and structural factors between the cities.