Injection drug use (IDU) into central veins, most common among long-term IDUs with no other options, can lead to severe infectious, vascular, and traumatic medical consequences. To follow-up on anecdotal reports of femoral vein injection and related medical problems in Seattle, we analyzed data from the annual survey of a community-based syringe exchange program. A total of 276 (81%) of 343 program attendees completed the survey in August 2010. Among 248 IDUs, 66% were male, 78% white, and 86% primarily injected opiates. One hundred respondents (40%) had injected into the femoral vein, 55% of whom were actively doing so, and 58% of whom reported medical complications that they attributed to the practice. Most (66%) used the femoral vein due to difficulty accessing other veins, although 61% reported other veins they could access and 67% reporting using other sites since initiating femoral injection. While injecting into muscle was more frequent among older IDUs with longer injection careers, the prevalence of femoral injection was highest among respondents in their late twenties with 2.5-6 years of injecting drugs. Multivariate analysis demonstrated an increased risk of initiating femoral injection each calendar year after 2007. Injecting into the femoral vein was also associated with white versus other race (odds ratio [OR] 2.7, 95% CI 1.3-5.4) and injection of primarily opiates versus other drugs (OR 6.3, 95% CI 1.2-32.9) and not associated with age, length of IDU career, or a history of injecting into muscle. These findings suggest a secular trend of increasing femoral injection among Seattle-area IDUs with a high rate of related medical problems. Interventions, such as education regarding the hazards of central venous injection and guidance on safe injection into peripheral veins, are needed to minimize the health consequences of femoral injection.