The purpose of this study was to evaluate the effect of carrier particle size and simulated inspiratory flow increase rate on emptying from dry powder inhalers (DPIs). Several flow rate ramps were created using a computer-generated voltage signal linked to an electronic proportioning valve with a fast response time. Different linear ramps were programmed to reach 30, 60, 90, and 120 L/minute over 1, 2, or 3 seconds. At the lower flow rates, 100-ms and 500-ms ramps were also investigated. Three DPIs, Spinhaler, Rotahaler, and Turbuhaler, were used to test the effect of flow rate ramp on powder emptying. To test the effect of carrier particle size, anhydrous lactose was sieved into 3 particle sizes, and 20 mg of each was introduced into #2 and #3 hard gelatin capsules for Spinhaler and Rotahaler, respectively. Emptying tests were also carried out using the on/off solenoid valve described in the United States. Pharmacopeia (USP) (resulting in no ramp generation). Powder emptying increased from 9% to 46% for Rotahaler and 69% to 86% for Spinhaler from the shallowest (3 seconds to reach peak flow) to the 100-ms ramp for the 53-to 75-μm lactose size range at 30 L/minute. Similar trends were observed for larger particle size fractions at the same flow rate. However, at higher airflow rates (60, 90, and 120 L/minute), there was no significant increase in percentage of emptying within the ramps for a particular particle size range. Trends observed were similar for placebo-filled Turbuhaler and commercially available Rotacaps used with Rotahaler, with the steepest ramp demonstrating more complete emptying. Percentage of powder emptying determined by the USP solenoid valve overestimated the emitted dose compared with the ramp method at 30 L/minute for all 3 devices. Results indicate that there is a significant difference in powder emptying at 30 L minute from the shallowest to the steepest ramp within a particular size range. Within a particular particle size range, the USP method produced more complete emptying than even the steepest ramp, especially at the lower flow rates. Thus, when the USP device is used to estimate DPI emptying at lower flow rates, the results are likely to overestimate DPI performance significantly.