The aldol condensation of acetaldehyde with other carbonyl molecules is a complex reaction wherein there is often formation of multiple undesirable side products. These side products include higher oligomers, which not only reduce the selectivity for the main product but also prevent the use of heterogeneous catalysts due to rapid deactivation. 3-Methylpent-3-en-2-one (MPO) is an important fine chemical used as a key intermediate in the fragrance and flavor industry and is produced by the aldol condensation of acetaldehyde (AcH) with methyl ethyl ketone (MEK). In this work, we investigate the continuous production of MPO in the presence of a cation exchange resin (Amberlyst-15) in a fixed-bed reactor. Our earlier work on batch kinetics reveals that a higher feed molar ratio of AcH:MEK results in a higher yield of MPO. Accordingly, reactions are performed in a laboratory fixed-bed reactor at different feed molar ratios, reaction temperatures, and residence times. The effect of side injection of acetaldehyde into the flow reactor was also investigated and found to favorably influence the selectivity toward MPO. A crucial observation was that maintaining a low concentration of acetaldehyde helps in reducing catalyst deactivation and hence extends its life. Based on the results obtained in the lab-scale reactor, MPO was successfully produced in the pilot-scale fixed-bed reactor by performing the reaction for an extended duration (570 h), indicating that the catalyst is sufficiently active under the conditions of interest without loss of activity. The intrinsic kinetic model developed earlier using the batch reactor data is incorporated in the fixed-bed reactor model and it was found that the predictions agree reasonably well with the experimental results. © 2021 American Chemical Society