The concerted photoreaction between trimethyl psoralen (TMP) and isomeric model compounds of oleic acid methyl ester (OAME) and eadilic acid methyl ester (EAME) are explored using density functional theory. The S₁ surfaces all reveal large barriers (25–31 kcal/mol) to reach the decay channels, whereas the S₂ surfaces differ considerably between the furan and pyrone side adducts. For the pyrone side adducts, a small barrier to reach the intersection between the S₁ and S₂ states is found, followed by a small second barrier on the S₁ surface to the low-lying decay channel. For the furan-side adducts, no such intersection between S₁ and S₂ is seen, which thus prevents these products from being formed in high yields. The photoinduced cycloaddition is more favorable between OAME and the pyrone side double bond of TMP than for any of the other systems, which agrees with the experimental findings that this is formed in the highest yield. The computed UV absorption spectra of TMP and the TMP(pyrone)-OAME cycloadduct agree well with the experimental spectra.