This article presents a method and guidance for quantifying the carbon footprint of clinical trials, developed by the Low Carbon Clinical Trials Group. The method involves creating a process map of clinical trial activities, identifying emission factors for each activity, and applying these to estimate the carbon footprint of specific trials. The guidance is intended to be used by trialists to identify carbon hotspots and inform lower carbon trial design. The study applied the method to two Cancer Research UK-funded trials: CASPS, an international phase 2 trial with 47 participants, and PRIMETIME, a UK-based phase 3 trial with 1962 patients. The carbon footprint of CASPS was estimated at 72 tonnes CO₂e, largely due to clinical trial unit emissions and staff travel. PRIMETIME had a carbon footprint of 89 tonnes CO₂e, mainly from trial-specific in-person participant assessments. The guidance includes a detailed method for calculating the carbon footprint of clinical trials, along with a data collation quick guide and worksheet. The guidance is designed to be used prospectively during the design phase of a trial before funding is secured. It accounts for the carbon footprint of clinical trials but does not include other metrics important for a full life cycle analysis, such as water use, land use, waste, and social and economic impacts. The study highlights the significant environmental impact of clinical trials, with the carbon footprint of all global trials estimated at around 27.5 million tonnes of CO₂e. The guidance aims to help trialists reduce the carbon footprint of their trials without compromising data quality, integrity, or validity. The guidance is currently being tested on a selection of trials from eight participating CTUs and is expected to be refined and expanded in the future. The results of the study demonstrate that clinical trials have a significant carbon footprint, with trial-specific activities such as meetings, travel, and data collection being major contributors. The guidance has been developed to help trialists identify and reduce these carbon hotspots. The study also emphasizes the need for further research to develop guidance on the interpretation of carbon footprinting results and to balance the impact of conducting a clinical trial against the potential benefits of the intervention. The guidance is intended to support various organizations, including universities, health service providers, and research funders, in meeting their carbon reduction commitments. The study concludes that the guidance is a crucial step towards achieving a more sustainable and responsible approach to clinical trials.This article presents a method and guidance for quantifying the carbon footprint of clinical trials, developed by the Low Carbon Clinical Trials Group. The method involves creating a process map of clinical trial activities, identifying emission factors for each activity, and applying these to estimate the carbon footprint of specific trials. The guidance is intended to be used by trialists to identify carbon hotspots and inform lower carbon trial design. The study applied the method to two Cancer Research UK-funded trials: CASPS, an international phase 2 trial with 47 participants, and PRIMETIME, a UK-based phase 3 trial with 1962 patients. The carbon footprint of CASPS was estimated at 72 tonnes CO₂e, largely due to clinical trial unit emissions and staff travel. PRIMETIME had a carbon footprint of 89 tonnes CO₂e, mainly from trial-specific in-person participant assessments. The guidance includes a detailed method for calculating the carbon footprint of clinical trials, along with a data collation quick guide and worksheet. The guidance is designed to be used prospectively during the design phase of a trial before funding is secured. It accounts for the carbon footprint of clinical trials but does not include other metrics important for a full life cycle analysis, such as water use, land use, waste, and social and economic impacts. The study highlights the significant environmental impact of clinical trials, with the carbon footprint of all global trials estimated at around 27.5 million tonnes of CO₂e. The guidance aims to help trialists reduce the carbon footprint of their trials without compromising data quality, integrity, or validity. The guidance is currently being tested on a selection of trials from eight participating CTUs and is expected to be refined and expanded in the future. The results of the study demonstrate that clinical trials have a significant carbon footprint, with trial-specific activities such as meetings, travel, and data collection being major contributors. The guidance has been developed to help trialists identify and reduce these carbon hotspots. The study also emphasizes the need for further research to develop guidance on the interpretation of carbon footprinting results and to balance the impact of conducting a clinical trial against the potential benefits of the intervention. The guidance is intended to support various organizations, including universities, health service providers, and research funders, in meeting their carbon reduction commitments. The study concludes that the guidance is a crucial step towards achieving a more sustainable and responsible approach to clinical trials.