Hydrodeoxygenation (HDO) of bio-oils obtained from intermediate pyrolysis with hot vapor filtration was investigated over Ru/C and NiCu/Al2O3 catalysts as a function of several parameters: feedstock (beech wood, wheat straw), pyrolysis temperature, catalyst and hydrotreatment temperature. Beech wood was found to be a suitable feedstock for HDO due to its low heteroatom content, whereas the high sulfur content in the wheat straw bio-oil caused irreversible poisoning of the catalysts. Ru/C generally consumed more hydrogen than NiCu/Al2O3, showing higher hydrogenation/HDO activity with higher selectivity towards alcohols and hydrocarbons, whereas NiCu/Al2O3 resulted in a higher concentration of ketones. The pyrolysis temperature affected the fragmentation degree; higher temperatures resulted in a higher quality pyrolysis oil with low oxygen mass fraction, but with decreased mass yield. By varying the hydrotreatment temperature (80, 150, 250, 350 °C), different classes of compounds were converted and different deoxygenation degrees were achieved. Overall the results indicate that intermediate pyrolysis with hot vapor filtration is a valid alternative to the more commonly used fast pyrolysis for decentralized (or small-scale) applications, especially for heterogeneous feedstocks with high ash content.