This study aimed to compare the efficiency of two methods for airborne surface decontamination: hydrogen peroxide vapor (HPV) and aerosolized hydrogen peroxide (aHP). Spores of G. stearothermophilus and B. atrophaeus were exposed to a 35% hydrogen peroxide solution under controlled laboratory conditions, including specific concentrations, exposure durations, humidity levels, and temperatures. Following each decontamination procedure, the spores were incubated for 7 days to evaluate bacterial growth and assess the efficacy of each method. The results indicate that the aHP method achieved biocidal rates of 84.76% for G. stearothermophilus and 89.52% for B. atrophaeus, while the HPV method demonstrated respective rates of 90.95% and 90.48%. These findings suggest that both the aHP and HPV methods are highly effective for microbial decontamination, with HPV showing a slight edge in overall efficacy. However, despite its comparable effectiveness, the HPV method has raised concerns regarding technical and economic factors. Observations highlighted issues such as fluctuations in humidity levels causing surface damage, a problem not encountered with the aHP method. Economically, HPV requires specific devices that can cost up to EUR 50,000, whereas aHP equipment costs do not exceed EUR 10,000. These observations emphasize the importance of critically evaluating the pros and cons of each decontamination method, taking into account factors such as biocidal efficacy, technical feasibility, and the associated costs.