The pyrolysis mechanisms of thiophene in asphaltenes have been investigated theoretically using density functional and ab initio quantum chemical techniques. All of the possible reaction pathways were explored using B3LYP, MP2, and CBS-QB3 models. A comparison of the calculated heats of reaction with the available experimental values indicates that the CBS-QB3 level of theory is quantitatively reliable for calculating the energetic reaction paths of the title reactions. The pyrolysis process is initiated via four different types of hydrogen migrations. According to the reaction barrier heights, the dominant 1,2-H shift mechanism involves two competitive product channels, namely, C2H2 CH2CS and CS + CH3CCH. The minor channels include the formation of CS + CH2CCH2, H2S + C4H2, HCS + CH2CCH, CS + CH2CHCH, H + C4H3S, and HS + C4H3. The methyl substitution effect was investigated with the pyrolysis of 2-methylthiophene and 3-methylthiophene. The energetics of such systems were very similar to that for unsubstituted thiophene, suggesting that thiophene alkylation may not play a significant role in the pyrolysis of asphaltene compounds.