A thiophene-fused BODIPY chromophore displays a large triplet-state quantum yield (ΦT = 63.7%). In contrast, when the two thienyl moieties are not fused into the BODIPY core, intersystem crossing (ISC) becomes inefficient and ΦT remains low (ΦT = 6.1%). First-principles calculations including spin-orbit coupling (SOC) were performed to quantify the ISC. We found larger SOC and smaller singlet-triplet energy gaps for the thiophene-fused BODIPY derivative. Our results are useful for studies of the photochemistry of organic chromophores.