Studies of the efficacy of heliox in patients with severe asthma have shown mixed results. Among the factors that are responsible for variable outcomes, the failure of heliox delivery systems to prevent room air entrainment (RAE) during β-agonist delivery is probably the most critical. While keeping the rotameter flow rate (FR) of heliox mixed 70:30 to a nebulizer at 10 L/min, the FR of heliox from a second gas source to a T-connector (TC) was increased during the delivery of the β-agonist with a conventional T-nebulizer delivery system (TNDS). A negative peak inspiratory flow (pneumotachometer reading) or a helium concentration of < 70% (quadralizer reading) were indicators of RAE. RAE was tested during spontaneous tidal breathing and acute asthma. A rotameter FR of 10 L/m to the nebulizer with no flow from a second gas source to a TC (conventional TNDS) resulted in a significant drop in helium concentration during tidal breathing (46.2%) and acute asthma (27.5%) due to RAE. This degree of helium dilution can negate the beneficial effects of heliox to lung mechanics almost completely. A rotameter FR of 10 L/m each to a nebulizer and a TC resulted in a helium concentration 69.8% during tidal breathing (no RAE), but 49% (significant RAE) during asthma events. A rotameter FR of 15 L/m (pressure regulator setting, 100 lbs per square inch) to a TC, while maintaining a rotameter FR of 10 L/m to a nebulizer prevented RAE during asthma (helium concentration, 69.9%). Conventional TNDS may be used to deliver the β-agonist with heliox during asthma without RAE.