A method for the analysis of the homologous series of alkanals, (E)-2-alkenals, and (E,E)-2,4-alkadienals is described utilizing a headspace solid-phase microextraction (HS-SPME) step and on-fiber derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) hydrochloride. Oxime derivatives formed on the fiber are desorbed in the gas chromatographic injector and analyzed by comprehensive 2-D GC coupled to quadrupole MS (GC×GC-qMS). Selecting specific fragment ions within the electron impact mass spectra of the oxime derivatives provides a suitable method for the target analysis of these aldehyde classes, which furthermore benefits from the increased separation efficiency by GC×GC. The analysis of higher molecular weight aldehydes is described in wine and grape seed oil as examples. Quantification of the aldehydes utilizes a stable isotope dilution analysis (SIDA) assay with octan-d16-al as isotopomeric internal standard. Besides the selectivity and sensitivity of aldehyde analysis using PFBHA derivatives, critical aspects on background level contamination and repeatability of the sample preparation method are discussed. Optimization of GC×GC-qMS parameters allowed a considerable saving of the cryogenic medium, involving additional (unmodulated) conditioning runs, rendering the method more amenable to routine analysis.