The use of oxygenated fuels decreases particulate matter (PM) emissions from diesel engines. Studies using engines, experimental flames, and modeling have shown that the decrease in soot emissions depends on the oxygenate molecular structure. To provide a better understanding of the complex processes occurring in engines leading to PM emissions, fundamental and systematic studies of the sooting tendency trends for diesel-range hydrocarbon-oxygenate blends are needed. We present a new approach to selecting fuel blends for sooting tendency measurements that minimizes the confounding effect of dilution of highly sooting components in the base fuel by maintaining constant concentrations of those components in the blends. This novel approach is illustrated by sooting tendency (smoke point) measurements in a diffusion flame for a variety of diesel-range hydrocarbonoxygenate blends with different molecular structures. The oxygenates included primary alcohols (1-butanol, 1-undecanol), diesters (dibutyl succinate, dibutyl maleate), esters (methyl decanoate and methyl oleate), and a glycol triether (tri(propylene glycol) methyl ether). The hydrocarbons included an aromatic (1,2,4-trimethylbenzene), a straight-chain alkane (n-hexadecane), and a highly branched alkane (2,2,4,4,6,8,8-heptamethylnonane). The fuels were investigated as three-component blends, with an oxygenate in a hydrocarbon base fuel consisting of a highly sooting hydrocarbon component (1,2,4-trimethylbenzene) and a low-sooting hydrocarbon (n-hexadecane). The oxygen-extended sooting index (OESI) provided sooting tendency trends that were generally consistent with expectations for both hydrocarbon-only and oxygenated fuels. The dominant chemical structure factors influencing the sooting tendency of the hydrocarbons were aromaticity and branching. For the oxygenates, the primary alcohols, the saturated monoester, and the glycol triether exhibited the lowest sooting tendency, followed by the shorter-chain diesters, and then the unsaturated monoester, with unsaturation increasing the sooting tendency.