The direct esterification of ibuprofen and methyl alpha-D-glucopyranoside in organic solvent by Novozym 435 was investigated in terms of the main variables controlling the process, including initial water activity (a(w), 0.05-0.75), incubation time, (0-168 h) and substrate concentration. The results showed that the lower initial aw values resulted in higher enzymatic activity and bioconversion yield. The most appropriate initial aw and incubation time were 0.06 and 144 h, respectively. The results also showed that the optimal ratio of ibuprofen to methyl alpha-D-glucopyranoside was 2.0. By optimizing these parameters, the yield increased about 50%. In addition, the product was confirmed to be methyl 6-O-(2'-(4'-isobutylphenyl) propionyl) D-alpha-glucopyranoside.