In the Seattle area men who have sex with men and also inject amphetamines (amphetamine-injecting MSM/IDU) are disproportionately likely to be infected with HIV. To characterize their distinctive characteristics, we combined data from two Seattle-area surveys of men who have sex with men (MSM) and two surveys of injection drug users (IDU). Amphetamine-injecting MSM/IDU were compared with: male IDU, MSM and other MSM/IDU. Amphetamine-injecting MSM/IDU were older than MSM but younger than IDU, more likely to be white than either group, and had an educational level higher than IDU but below MSM. They had the highest HIV prevalence (56 vs. 4–19 %). However, reported HIV cases among them fell from 92 in 1990 to 25 in 2012. They were most likely to report ten or more sex partners (49 vs. 4–26 %), an STD diagnosis (22 vs. 1–7 %) and be tested for HIV (odds ratio 1.00 vs. 0.34–0.52), and least likely to share needles (odds ratio 1.00 vs. 6.80–10.50). While sexual risk remains high, these data suggest measurable and effective risk reduction with respect to sharing injection equipment and HIV testing among Seattle-area amphetamine-injecting MSM/IDU.