We have used Density Functional Theory to model the mixed aldol condensation reaction catalyzed by acidic zeolites. We have studied the convergence of barriers for the keto-enol tautomerization of acetone in cluster models of HZSM-5 and HY ranging in size from 3-37T. A key finding was that activation barriers for keto-enol tautomerization of acetone in both zeolites (~20 kcal/mol) are significantly higher than those for the condensation reaction between the acetone enol and formaldehyde in 11T cluster models of HZSM-5 and HY. Moreover we found that three zeolite clusters of HZSM-5, similarly sized but including different structural features of the zeolite framework, gave very different activation barriers. These results indicated that a more rigorous approach to constructing cluster models of zeolites was needed. We have developed two different approaches to build cluster models of zeolites and used two acid-zeolite-catalyzed processes related to the conversion of biomass as platforms to systematically investigate cluster-size convergence. Our central finding is that clusters generated with multi-centered spherical cutoffs yield converged reaction energies with smaller system sizes than clusters generated by counting framework bonds. The delta approach to constructing finite clusters of zeolite crystals provides a well-defined prescription and employs a single length scale (d = 5 Å) to converge reaction energies to within chemical accuracy (±1 kcal/mol). Although reaction energies were convergent at d = 5 Å, it is not clear that a single length scale is sufficient to converge activation barriers. We used two reaction systems as platforms to establish convergence of activation barriers using delta clusters. We find that a δ ≥ 4 Å cutoff is sufficient to converge activation barriers to within chemical accuracy (±1 kcal/mol). After convergence was established, we studied the acid-zeolite-catalyzed mixed aldol condensation of acetone with more biomass-relevant aldehydes, such as hydroxymethyl furfural and furfural, in δ = 4 Å clusters of HZSM-5. We have found that the mechanism for condensation in HZSM-5 is concerted, unlike that of the homogeneous acid catalyzed mechanism. Ultimately, we conclude that the keto/enol tautomerization of acetone remains rate-determining in the case of condensation with formaldehyde, furfural or hydroxymethyl furfural in HZSM-5.