The synthesis of solketal from acetone and glycerol (I) was investigated in the presence of the isostructural MOFs of the families MIL-100(M) and MIL-53(M) (M = V, Al, Fe and Cr) and mixed MIL-53(Al,V) (Al/V – 100/0, 75/25, 50/50, 25/75 and 0/100 atom/atom). The main products were a five-membered solketal (2,2-dimethyl-1,3-dioxane-4-methanol, (II)) and a six-membered acetal (2,2-dimethyl-dioxane-5-ol, (III)). It was demonstrated that the reaction rate and isomer selectivity depend on different parameters such as the type of metal ion, the length of the M-O bond, the rate constant for the exchange of the water molecules from the first coordination sphere of a metal ion and the value of the zero point of the surface charge (pHPZC). Investigation of mixed MIL-53(Al,V) shows that the reaction rate and selectivity towards (II) increase with increasing V3+ content in MIL-53(Al,V). V-containing MOFs possess a high activity and selectivity at 25 °C. The efficiencies of MIL-100(V) and MIL-47(V) were higher than those of H2SO4, SnCl2 and p-toluenesulfonic acid at 25 °C. The MIL-100(V) catalyst showed good reusability for 4 catalyst recycles.