This article describes a new method for (1) systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing work sites, and (2) evaluating intervention effectiveness. We developed a checklist containing six unique sets of yes/no variables organized in a 2 x 3 matrix of exposure potential versus protection (two columns) at the levels of materials, processes, and human interface (three rows). The three levels correspond to a simplified hierarchy of controls. Each of the six sets of indicator variables was reduced to a high/moderate/low rating. Ratings from the matrix were then combined to generate a single overall exposure prevention rating for each area. Reflecting the hierarchy of controls, material factors were weighted highest, followed by process, and then human interface. The checklist was filled out by an industrial hygienist while conducting a walk-through inspection (N = 131 manufacturing processes/areas in 17 large work sites). One area or process per manufacturing department was assessed and rated. Based on the resulting Exposure Prevention ratings, we concluded that exposures were well controlled in the majority of areas assessed (64% with rating of 1 or 2 on a 6-point scale), that there is some room for improvement in 26 percent of areas (rating of 3 or 4), and that roughly 10 percent of the areas assessed are urgently in need of intervention (rated as 5 or 6). A second hygienist independently assessed a subset of areas to evaluate inter-rater reliability. The reliability of the overall exposure prevention ratings was excellent (weighted kappa = 0.84). The rating scheme has good discriminatory power and reliability and shows promise as a broadly applicable and inexpensive tool for intervention needs assessment and effectiveness evaluation. Validation studies are needed as a next step. This assessment method complements quantitative exposure assessment with an upstream prevention focus.