The carbonyls formaldehyde, acetaldehyde, and crotonaldehyde are on the FDA list of Harmful and Potentially Harmful Constituents (HPHCs) found in tobacco products. As mandated by the Family Smoking Prevention and Tobacco Control Act, tobacco manufacturers and importers are required to report quantities of HPHCs to the United States Food and Drug Administration (FDA). Currently no standardized method exists for the determination of these carbonyls in smokeless tobacco products (STPs). The objective of this study was to compare two commonly used analytical platforms, gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-ultraviolet detection (HPLC-UV), for the determination of these carbonyls in snus, moist smokeless tobacco (MST), dry snuff, and chewing tobacco. The GC-MS procedure used O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA) derivatization as compared to the 2,4-dinitrophenylhydrazine (DNPH) derivatization used with the HPLC-UV procedure. The extraction and derivatization steps were evaluated for stability of the carbonyl yields for CORESTA reference tobacco products CRP1, CRP2, CPR3, CRP4 as well as 3R4F tobacco filler samples. The PFBHA derivatization used with the GC-MS method showed greater analyte stability as compared to the DNPH derivatization. Furthermore, the GC-MS method had inherently greater selectivity due to mass spectrometry detection as well as greater sensitivity afforded by selected ion monitoring (SIM).