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Background: Among the four bases, guanine is the most susceptible to damage from oxidative stress. Replication of DNA containing damaged guanines results in G to T mutations. Therefore, the mutations resulting from oxidative DNA damage are generally expected to predominantly consist of G to T (and C to A when the damaged guanine is not in the reference strand) and result in decreased GC content. However, the opposite pattern was reported 16 years ago in a study of prokaryotic genomes. Although that result has been widely cited and confirmed by nine later studies with similar methods, the omission of the effect of shared ancestry requires a re-examination of the reliability of the results., Results: When aerobic and obligate aerobic prokaryotes were mixed together and anaerobic and obligate anaerobic prokaryotes were mixed together, phylogenetic controlled analyses did not detect significant difference in GC content between aerobic and anaerobic prokaryotes. This result is consistent with two generally neglected studied that had accounted for the phylogenetic relationship. However, when obligate aerobic prokaryotes were compared with aerobic prokaryotes, anaerobic prokaryotes, and obligate anaerobic prokaryotes separately using phylogenetic regression analysis, a significant positive association was observed between aerobiosis and GC content, no matter it was calculated from whole genome sequences or the 4-fold degenerate sites of protein-coding genes. Obligate aerobes have significantly higher GC content than aerobes, anaerobes, and obligate anaerobes., Conclusions: The positive association between aerobiosis and GC content could be attributed to a mutational force resulting from incorporation of damaged deoxyguanosine during DNA replication rather than oxidation of the guanine nucleotides within DNA sequences. Our results indicate a grade in the aerobiosis-associated mutational force, strong in obligate aerobes, moderate in aerobes, weak in anaerobes and obligate anaerobes.