The Ontario Prehospital Advanced Life Support (OPALS) Study represents the largest prehospital study yet conducted, worldwide. This study will involve more than 25,000 cardiac arrest, trauma, and critically ill patients over an 8-year period (1994-2002). The current article, Part II, describes in detail the rationale and methodology for major trauma and respiratory distress patients and for an economic evaluation of Advanced Life Support (ALS) programs in the OPALS Study. The OPALS Study, using a rigorous controlled methodology and a large sample size, should clearly indicate the benefit in trauma and respiratory distress patient survival and morbidity that results from the widespread introduction of prehospital ALS programs to communities of many different sizes. [Stiell IG, Wells GA, Spaite DW, Nichol G, O'Brien B, Munkley DP, Field BJ, Lyver MB, Luinstra LG, Dagnone E, Campeau T, Ward R, Anderson S, for the OPALS Study Group: The Ontario Prehospital Advanced Life Support (OPALS) Study Part II: Rationale and methodology for trauma and respiratory distress patients.