Abstract Background Endotracheal intubation remains the definitive skill needed for airway management of both medical and surgical patients treated in the prehospital and hospital arenas. Subsequently, rapid sequence intubation (RSI) protocols have been established for various first-line emergency service providers. Because RSI results in the paralysis of skeletal muscles, with a subsequent period of apnea and an increased potential for oxygen desaturation, the accuracy of pulse oximetry (SpO2) data is critical in guiding pre-oxygenation efforts and indicating abandonment of intubation attempts to avoid hypoxic injury. Latency of up to 120 s has been demonstrated in conditions producing peripheral vasoconstriction. The influence of peripheral oximetry on the decision-making process during the establishment of a definitive airway has not, to our knowledge, been previously investigated in the prehospital setting. Objective To demonstrate how signal latency may manifest itself as a perceived oxygen desaturation with a subsequent premature abortion of a primary RSI attempt or erroneous extubation. Case Examples We document endotracheal extubation associated with pulse oximetry signal latency during prehospital RSI with the use of digital SpO2 probes. Two case examples are presented that are taken from a retrospective analysis of pre-hospital RSI data recorded by the City of San Diego Emergency Medical Services. Conclusion To avoid the possibility of mistaking oximetry signal latency for oxygen desaturation during pre-hospital RSI, we propose a conservative approach of aggressive pre-oxygenation to SpO2 values≥94%, and the use of quantitative continuous capnometry for decision-making regarding whether the endotracheal tube is correctly placed. In cases of hypoxemia despite a properly placed tube, focus should be turned to other causes of post intubation hypoxemia.