Some prior research in office buildings has associated higher indoor temperatures even within the recommended thermal comfort range with increased worker symptoms. We reexamined this relationship in data from 95 office buildings in the U.S. Environmental Protection Agency's Building Assessment Survey and Evaluation (BASE) Study. We investigated relationships between building-related symptoms and thermal metrics constructed from real-time measurements. We estimated odds ratios (ORs) and 95% confidence intervals in adjusted logistic regression models with general estimating equations, overall and by season. Winter indoor temperatures spanned the recommended winter comfort range; summer temperatures were mostly colder than the recommended summer range. Increasing indoor temperatures, overall, were associated with increases in few symptoms. Higher winter indoor temperatures, however, were associated with increases in all symptoms analyzed. Higher summer temperatures, above 23°C, were associated with decreases in most symptoms. Humidity ratio, a metric of absolute humidity, showed few clear associations. Thus, increased symptoms with higher temperatures within the thermal comfort range were found only in winter. In summer, buildings were overcooled, and only the higher observed temperatures were within the comfort range; these were associated with decreased symptoms. Confirmation of these findings would suggest that thermal management guidelines consider health effects as well as comfort.Practical Implications: In winter, higher temperatures within the thermal comfort range are common in U.S. office buildings and may be associated with increased symptoms. In summer, temperatures below the thermal comfort range are common and may be associated with increased symptoms. Results from this large study thus suggest that in U.S. office buildings, less winter heating (in buildings that are in heating mode) and less summer cooling may reduce acute symptoms while providing substantial energy conservation benefits, with no expected thermal comfort penalty and, in summer, even thermal comfort benefits. If confirmed, this would be welcome news.