Propranolol, ((R,S)-1-iso-propylamino-3-(1-naphthoxy)-2-propanol), is a β-adrenergic antagonist and is commercially available as a racemic mixture. Only the S-enantiomer has the desired therapeutic effect. Therefore, many researchers have been working on strategies to obtain S-propranolol with high enantiomeric purity. One approach to carry out the acetylation of (R,S)-Propranolol using Candida antarctica lipase B, CalB. This reaction leads to an enantiomeric purity of 96% at a relatively low conversion rate of 30 %. In our research group, we have been studying this reaction. The CalB active site is composed by the triad catalytic (ASP 187, HIS 224 and SER 105) and oxyanion hole (GLN 106 and THR 40). In a previous work, a QM/MM (Quantum Mechanics / Molecular Mechanics) study was carried out, using a QM region consisting only of the catalytic triad of CalB and (R,S)-propranolol [1]. In the present study, we investigate the effect of expanding the quantum region to include the oxyanion hole and to comprehend the effect of intermolecular hydrogen bonds present between the (R,S)-propranolol and the CalB active site. The electronic structure was analyzed using the Quantum Theory of Atoms In Molecules, QTAIM. Our results show that: 1. the studied reactions are more exothermic with the inclusion of the oxyanion hole than with only the catalytic triad. 2. the intermolecular interactions between (R,S)-propranolol and the CalB active site are dominated by hydrogen bonds (HB). Among those HBs, only one between propranolol and HIS 224, and another one between THR 40 and the carbonyl oxygen of acetylated SER 105 play an important role.