The myriad benefits obtained from regular sustained exercise are undeniable. However, in a small fraction of otherwise healthy avid exercisers, there may be an increased risk for venous thromboembolism or blood clot(s) following endurance exercise. Since 2009, our research group has conducted studies using the Boston and Hartford marathons as our research laboratory to examine this phenomenon. Marathon-based field studies allow for the collection of data under free-living conditions that would otherwise not be possible to conduct in a laboratory setting. The present case study details the many carefully thought-out methodological and logistical considerations taken throughout our most recent prospective, field-based, randomized-controlled study conducted at the 2015 Boston Marathon. Some key lessons learned from our experiences are specific to marathon-based field studies. However, several lessons learned may be extrapolated to inform possible considerations while conducting a fast-paced, randomized-controlled, field study, more generally. These include possible biases inherent in a group, field-based versus individual laboratory study design; the importance of detail in standardizing screening, randomization, data collection, and study wrap up procedures; the potential consequences of failing to allocate funds for unforeseen expenses; and the impact of establishing a strong rapport with research participants.