Individuals with hoarding disorder (HD) have difficulty parting with personal possessions, which leads to the accumulation of excessive clutter. According to a proposed biphasic neurobiological model, HD is characterized by blunted central and peripheral nervous system activity at rest and during neutral (non-discarding) decisions, and exaggerated activity during decision-making about discarding personal possessions. Here, we compared the error-related negativity (ERN) and psychophysiological responses (skin conductance, heart rate and heart rate variability, and end tidal CO2) during neutral and discarding-related decisions in 26 individuals with HD, 37 control participants with anxiety disorders, and 28 healthy control participants without psychiatric diagnoses. We also compared alpha asymmetry between the HD and control groups during a baseline resting phase. Participants completed a series of Go/No Go decision-making tasks, one involving choosing certain shapes (neutral task) and the other involving choosing images of newspapers to imaginally “discard” (discarding task). Contrary to hypotheses, there were no group differences in the ERN or any psychophysiological measures. Alpha asymmetry at rest did not differ between groups. The findings suggest that the ERN and psychophysiological responses may not differ in individuals with HD during simulated discarding decisions relative to control participants, although the null results may be explained by methodological challenges in using Go/No Go tasks as discarding tasks. Future replication and extension of these results will be needed using ecologically valid discarding tasks.