Introduction We developed evidence-based recommendations for prehospital evaluation and treatment of adult patients with respiratory distress. These recommendations are compared with current protocols used by the 33 local emergency medical services agencies (LEMSA) in California. Methods We performed a review of the evidence in the prehospital treatment of adult patients with respiratory distress. The quality of evidence was rated and used to form guidelines. We then compared the respiratory distress protocols of each of the 33 LEMSAs for consistency with these recommendations. Results PICO (population/problem, intervention, control group, outcome) questions investigated were treatment with oxygen, albuterol, ipratropium, steroids, nitroglycerin, furosemide, and non-invasive ventilation. Literature review revealed that oxygen titration to no more than 94–96% for most acutely ill medical patients and to 88–92% in patients with acute chronic obstructive pulmonary disease (COPD) exacerbation is associated with decreased mortality. In patients with bronchospastic disease, the data shows improved symptoms and peak flow rates after the administration of albuterol. There is limited data regarding prehospital use of ipratropium, and the benefit is less clear. The literature supports the use of systemic steroids in those with asthma and COPD to improve symptoms and decrease hospital admissions. There is weak evidence to support the use of nitrates in critically ill, hypertensive patients with acute pulmonary edema (APE) and moderate evidence that furosemide may be harmful if administered prehospital to patients with suspected APE. Non-invasive positive pressure ventilation (NIPPV) is shown in the literature to be safe and effective in the treatment of respiratory distress due to acute pulmonary edema, bronchospasm, and other conditions. It decreases both mortality and the need for intubation. Albuterol, nitroglycerin, and NIPPV were found in the protocols of every LEMSA. Ipratropium, furosemide, and oxygen titration were found in a proportion of the protocols, and steroids were not prescribed in any LEMSA protocol. Conclusion Prehospital treatment of adult patients with respiratory distress varies widely across California. We present evidence-based recommendations for the prehospital treatment of undifferentiated adult patients with respiratory distress that will assist with standardizing management and may be useful for EMS medical directors when creating and revising protocols.