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Work-related fatigue of the lower extremities is a known cause of lost productivity and significant employer costs. Common workplace solutions to reduce fatigue levels include anti-fatigue matting, shoe orthoses, or sit/stand work stations. However, assessment of these anti-fatigue measures within the workplace has been limited.This was a cross sectional study in an automotive assembly plant on employees with at least 6 months tenure. Subject data were collected via questionnaires including Likert-scale questions to define fatigue severity. Jobs were evaluated for lower extremity ergonomic exposures via videotaping, pedometers, interviews, and industrial engineering records.Lower extremity fatigue at the end of the work day was associated with a higher prevalence of smoking, rheumatoid arthritis, job dissatisfaction, use of shoes with firmer outsoles, and increased time on the job spent standing or walking. Supervisor support and increased time spent on carpet were protective. Lower extremity fatigue that interfered with activities outside of work had additional risk factors including higher BMI, prior diagnosis of osteoarthritis, and increased hours per week spent working.While these results identify carpet as being protective against lower extremity fatigue, no similar relationship was identified for anti-fatigue mats. No adverse relationship was found between hard surfaces such as concrete and lower extremity fatigue. Given the high costs associated with work-related fatigue, future areas for potential intervention include smoking cessation, specific shoe recommendations, and enhancing psychosocial aspects of work such as supervisor support. Am. J. Ind. Med. 54:216-223, 2011. © 2010 Wiley-Liss, Inc.