Several factors may alter apparent resting metabolic rate (RMR) during measurement with indirect calorimetry. Likewise, numerous indirect calorimetry measurement protocols have been developed over the years, and the methodology employed could influence test results. As part of a larger project to determine the role of indirect calorimetry in clinical practice, a systematic review of the literature was undertaken to determine the ideal subject condition and test methodology for obtaining reliable measurement of RMR with indirect calorimetry. Food, ethanol, caffeine, and nicotine affect RMR for a variable number of hours after consumption; therefore, intake of these items must be controlled before measurement. Activities of daily living increase metabolic rate, but a short rest (< or =20 minutes) before testing is sufficient for the effect to dissipate. Moderate or vigorous physical activity has a longer carryover effect and therefore must be controlled in the hours before a measurement of RMR is attempted. Limited data were found regarding ideal ambient conditions for RMR testing. Measurement duration of 10 minutes with the first 5 minutes deleted and the remaining 5 minutes having a coefficient of variation <10% gave accurate readings of RMR. Individuals preparing for RMR measurement via indirect calorimetry should refrain from eating, consuming ethanol and nicotine, smoking, and engaging in physical activity for varying times before measurement. The test site should be physically comfortable and the individual should have 10 to 20 minutes to rest before measurement commences. A 10-minute test duration with the first 5 minutes discarded and the remaining 5 minutes having a coefficient of variation of <10% will give an accurate measure of RMR.