‘Primary’ blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. With continued experimental focus on PBI mechanisms, recently on blast traumatic brain injury, meaningful test outcomes rely on appropriate simulated conditions. Selected PBI predictive criteria (grouped into those affecting the auditory system, pulmonary injuries and brain trauma) are combined and plotted to provide rationale for generating clinically relevant loading conditions. Using blast engineering theory, explosion characteristics including blast wave parameters and fireball dimensions were calculated for a range of charge masses assuming hemispherical surface detonations and compared with PBI criteria. While many experimental loading conditions are achievable, this analysis demonstrated limits that should be observed to ensure loading is clinically relevant, realistic and practical. For PBI outcomes sensitive only to blast overpressure, blast scaled distance was demonstrated to be a useful parameter for guiding experimental design as it permits flexibility for different experimental set-ups. This analysis revealed that blast waves should correspond to blast scaled distances of 1.75<Z<6.0 to generate loading conditions found outside the fireball and of clinical relevance to a range of PBIs. Blast waves with positive phase durations (2–10 ms) are more practical to achieve through experimental approaches, while representing realistic threats such as improvised explosive devices (ie, 1–50 kg trinitrotoluene equivalent). These guidelines can be used by researchers to inform the design of appropriate blast loading conditions in PBI experimental investigations.