For applications in ultrafiltration membranes, cancer cell uptake, bioimaging, and diagnostics, a reverse dissolution approach, where swollen poly(vinyl alcohol) (PVA) particles are added to a butyraldehyde solution in ethanol, is employed to synthesize poly(vinyl bytyral) (PVB) with high contents of butyral groups. The final butyral group content (up to 84%) of PVB is found to be dependent strongly on the initial condensed state of PVA, the degree of polymerization of PVA, the purity and volume of ethanol, and the pH value. A maximum of butyral group content may be obtained under conditions: swollen PVA particles, (95 vol %) ethanol of 125-150 mL, and pH 1. This reverse dissolution approach has advantages such as a mild reaction condition (70 degrees C), no predissolution of PVA at high temperatures, no vacuum removal of water during reaction, and low water consumption in post-treatment of the product.