The Premarket Tobacco Product Application (PMTA) process for ENDS recommends that a wide range of Harmful and Potentially Harmful Compounds (HPHCs) be determined to support the application. The U.S. Food and Drug Administration provides guidance specifying a number of constituents and chemicals that should be included for analysis. However, no guidance is provided on appropriate analytical methodologies or test procedures. The majority of published literature reports targeted compound yields using collection of a single puff block, often 50 puffs, or collection of multiple puff blocks over a single sample. In this study, first 50-puff collection was compared to whole pod measurement (WPM), using 1-end of pod life collections. Data was collected under both ISO20768 (55/3/30) and intense (110/6/30) puffing regimes, using eight commercially marketed products from a number of manufacturers. Yields were normalized to total device mass loss. Analytes included primary constituents, carbonyls, metals, and glycidol. Two limitations of the first 50-puff approach were identified: (1) some targeted analytes, i.e. carbonyls, were found to be non-linear with aerosol yield over the entire pod life, thus whole pod yield could not be determined from 50-puff measurements, and (2) WPM improved the method limit of detection (LOD) and limit of quantitation (LOQ) by five-fold or more, compared to 50-puff, due to increasing collected aerosol mass. As such, some analytes that were below LOD/LOQ for 50-puffs, were found to be reportable (>LOQ) with WPM. Formaldehyde, acetaldehyde, acrolein, and diacetyl showed significant differences between collection approaches, with up to 500 % difference observed in analytical results. This study confirms that WPM improves the accuracy of carbonyl and other analyte yields for all ENDS products tested.