BACKGROUND Occupational exposure to methylene bisphenyl isocyanate (MDI) presents serious worker health concerns as it may lead to short- and long-term health effects such as asthma, airway irritation, hypersensitivity pneumonitis, and irritation of skin and mucous membranes. While studies of worker isocyanate exposures during vehicle painting activities are widespread, few studies have investigated the spray-on truck bed-liner (STBL) industry. The purpose of this study was to determine the effectiveness of several ventilation system variables and process characteristics in controlling MDI concentrations in the STBL industry. METHODS A total of 47 personal air samples were collected for MDI during 18 site visits at nine STBL companies in Colorado and Wyoming. Ventilation system and process characteristics that were assessed included: ventilation system face velocity, airflow, air changes per minute (AC/M), capture velocity, percent of MDI in bed-liner product, application temperature, application pressure, paint booth temperature, paint booth relative humidity, paint booth volume, and quantity of bed-liner product applied. RESULTS Pearson correlation revealed percentage of MDI in bed-liner product (r = 0.557, n = 14, P < 0.05) and process temperature (r = 0.677, n = 14, P < 0.05) had high positive correlation with MDI concentration. Ventilation system face velocity (r = -0.578, n = 14, P < 0.05) and AC/M (r = -0.657, n = 14, P < 0.05) had high negative correlation with MDI concentration while airflow (r = -0.475, n = 14, P < 0.05) and capture velocity (r = -0.415, n = 14, P = 0.07) had moderate negative correlation with MDI concentration. Multiple linear regression revealed process temperature and capture velocity made a statistically significant and unique contribution in estimating MDI concentration (F (2, 11) = 10.99, P < 0.05) with an adjusted R2 of 0.61, explaining 61% of the variability in MDI concentration. CONCLUSIONS This investigation contributed to an understudied STBL industry by targeting determinants germane to MDI exposures during STBL application processes. Increasing ventilation performance for AC/M, airflow, face velocity, and capture velocity while also decreasing bed-liner application temperature and bed-liner product MDI content may have the greatest effect on reducing worker MDI exposures during STBL activities.