Introduction: Exposure to metals and solvents have been proposed as a risk factor for neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), however research has been complicated by difficulty in assessing historical exposures. Methods: Incident ALS cases and matched controls were recruited over 4 years in Ireland, Italy and the Netherlands. Trained investigators carried out structured interviews of participants to gather details of lifetime occupational history. JobExposure-Matrices (JEM) were applied to occupational data to characterize risk of exposure to pesticides. Logistic regression models adjusting for age, gender, education and cohort were used to determine the association between metal and solvent exposure and ALS risk. Results: 1,557 patients and 2,922 controls were included. We found increased odds ratios (ORs) for ALS with any history of exposure to any airborne metals (OR = 1.25 95% CI: 1.05 – 1.49) and benzene (OR = 1.23 95%CI: 1.06 – 1.43). These findings were robust to sensitivity analyses, and were unchanged after correction for physical activity, smoking and alcohol consumption. Increased odds for exposure to chromium (OR = 1.29 95% CI: 1.02 – 1.64) and aromatic solvents (OR 1.17 95%CI: 1.00 – 1.36) were found only after adjustment for multiple confounders. Discussion: Our findings provide new evidence for an association between metals and solvent exposure and ALS in European populations. Further work is ongoing to identify any population specific differences and exposure-response relationships.