BACKGROUND: All sectors of the economy, including the health research sector, must reduce their carbon emissions. The UK National Institute for Health Research has recently prepared guidelines on how to minimize the carbon footprint of research. We compare the carbon emissions from two international clinical trials in order to identify where emissions reductions can be made. METHODS: We conducted a carbon audit of two clinical trials (the CRASH-1 and CRASH-2 trials), quantifying the carbon dioxide emissions produced over a one-year audit period. Carbon emissions arising from the coordination centre, freight delivery, trial-related travel and commuting were calculated and compared. RESULTS: The total emissions in carbon dioxide equivalents during the one-year audit period were 181.3 tonnes for CRASH-1 and 108.2 tonnes for CRASH-2. In total, CRASH-1 emitted 924.6 tonnes of carbon dioxide equivalents compared with 508.5 tonnes for CRASH-2. The CRASH-1 trial recruited 10,008 patients over 5.1 years, corresponding to 92 kg of carbon dioxide per randomized patient. The CRASH-2 trial recruited 20,211 patients over 4.7 years, corresponding to 25 kg of carbon dioxide per randomized patient. The largest contributor to emissions in CRASH-1 was freight delivery of trial materials (86.0 tonnes, 48% of total emissions), whereas the largest contributor in CRASH-2 was energy use by the trial coordination centre (54.6 tonnes, 30% of total emissions). CONCLUSIONS: Faster patient recruitment in the CRASH-2 trial largely accounted for its greatly increased carbon efficiency in terms of emissions per randomized patient. Lighter trial materials and web-based data entry also contributed to the overall lower carbon emissions in CRASH-2 as compared to CRASH-1. TRIAL REGISTRATION NUMBERS: CRASH-1: ISRCTN74459797CRASH-2: ISRCTN86750102.