A novel horizontal reactive distillation apparatus and a new overall process scheme are proposed for continuous multicomponent chiral resolution via reversible enantioselective acylation of a chiral (racemic) substrate by a chiral (racemic) acyl donor. The process enables simultaneous production of up to four enantiomers with enhanced chiral purity. Kinetic studies, miniplant experiments, and process simulation results are described for a model lipase-catalyzed reaction: (R)-enantioselective transesterification of (R,S)-1-n-butoxy-2-propanol with (R,S)-1-methoxy-2-acetoxypropane to produce (R)-1-n-butoxy-2-acetoxypropane, (R)-1-methoxy-2-propanol, and the two unreacted (S)-enantiomers of the (R,S)-reagents. A horizontal, compartmentalized reactive distillation vessel is specified instead of a conventional reactive distillation column to provide longer liquid-phase residence time needed for adequate conversion. Low vapor-traffic pressure drop allows operation under vacuum at reduced temperatures for good enzyme stability and enantioselectivity. The general technology has potential as a means to producing a wide range of chiral synthons used in asymmetric syntheses of chiral pharmaceuticals and other biologically active products. (c) 2013 American Institute of Chemical Engineers AIChE J, 59: 2603-2620, 2013