The performance of pyrolysis oil in a large-scale combustion system is investigated to determine the feasibility of displacing fuel oil or natural gas in current heating and power infrastructure. A commercial 600 kW building heating boiler was installed and retrofitted to burn pyrolysis oil and pyrolysis oil mixtures at controlled conditions. The boiler was equipped with the necessary fuel systems and instrumentation to enable accurate and independent control of the pilot light, natural gas flow, and liquid fuel system parameters, while maintaining standard boiler safety cutouts. Exhaust analysis equipment was installed to allow measurements of particulate matter (PM), NO, CO, and unburned hydrocarbons (HC). Shadowgraphy spray imaging and phase-Doppler particle analysis (PDPA) was performed on non-reacting fuel sprays to investigate atomization phenomena. Ethanol was mixed with the pyrolysis oil at various concentrations and tested to determine the ideal concentration for spay and combustion performance. Combustion tests were conducted in the boiler using #2 fuel oil, natural gas, pyrolysis oil, and mixtures of ethanol and pyrolysis oil. Ethanol pyrolysis oil mixtures were primarily investigated while varying nozzles and nozzle conditions, overall equivalence ratio, and ethanol content of the mixture utilizing a natural gas pilot light and a natural gas co-fire to increase flame stability and broaden the range of stable conditions. Combustion results showed very high emissions with a pressure atomizing nozzle and low emissions with an air atomized nozzle, agreeing with spray imaging results. By optimizing atomization air pressure and equivalence ratio, PM, CO, and HC were brought down to levels near typical fuel oil combustion emissions with ethanol content as low as 20%. NO was relatively unaffected by nozzle conditions, equivalence ratio, and ethanol content. These data show the feasibility, range of conditions, and fuel injection strategies for clean combustion of bio-oil and displacement of natural gas or fuel oil in large-scale commercial boilers.