BACKGROUND: Methamphetamine injection is associated with disease outcomes that may be amplified by environmental toxicants such as metals contaminating methamphetamine preparations. This study evaluates how exposure to metals and Pb accumulation vary relative to filtration practices among Indigenous people who inject methamphetamine. METHODS: A cross-sectional survey of 100 Fort Peck Tribal members (60 people who inject methamphetamine, 40 referents) was conducted. Questionnaires were administered, and portable x-ray fluorescence measured Pb in tibial bones, metals in used syringes, and seized methamphetamine. RESULTS: Mean tibial bone Pb concentration did not vary between referents (13.1μg/g, 95 % CI: 11.2-14.9) and people who inject methamphetamine (12.1μg/g, 95 % CI: 10.9-13.3), but an interaction effect suggests that years of injection methamphetamine use across the lifespan is positively associated with tibial bone Pb concentration when filtration methods were not reported. In used syringes, Copper (Cu), Zinc (Zn), Tungsten (W), Nickel (Ni), and Mercury (Hg) mercury were detected. Participants who filtered their injection preparation had a lower mean number of metals detected in their syringes (0.19, 95 % CI: -0.06-0.45) compared to non-filterers (0.65, 95 % CI: 0.22-1.08). Zn and Ni were detected in seized methamphetamine samples provided by local law enforcement. CONCLUSIONS: Significant variation in metals was detected between filterers and nonfilterers. More research on optimizing filtration techniques to remove metals is warranted.