Immobilized Candida antarctica lipase B, Novozym 435, was used as the biocatalyst in the esterification of adipic acid with four different isomers of butanol (n-butanol, sec-butanol, iso-butanol, and tert-butanol). Optimum conditions for the synthesis of adipate esters were obtained using response surface methodology approach with a four-factor-five-level central composite design concerning important reaction parameters which include time, temperature, substrate molar ratio, and amount of enzyme. Reactions under optimized conditions has yielded a high percentage of esterification (>96%) for n-butanol, iso-butanol, and sec-butanol, indicating that extent of esterification is independent of the alcohol structure for primary and secondary alcohols at the optimum conditions. Minimum reaction time (135 min) for achieving maximum ester yield was obtained for iso-butanol. The required time for attaining maximum yield and also the initial rates in the synthesis of di-n-butyl and di-sec-butyl adipate were nearly the same. Immobilized Candida antarctica lipase B was also capable of esterifying tert-butanol with a maximum yield of 39.1%. The enzyme is highly efficient biocatalyst for the synthesis of adipate esters by offering a simple production process and a high esterification yield.