We propose an empirical rule that predicts which enantiomer of a primary alcohol reacts faster in reactions catalyzed by lipase from Pseudomonas cepacia (PCL). This rule, based on the size of the substituents at the stereocenter, shows an 89% reliability (correct for 54 of 61 examples). This rule is not reliable for primary alcohols that have an oxygen atom attached to the stereocenter; we excluded these alcohols from the tally above. Surprisingly, the sense of enantiopreference of PCL toward primary alcohols is opposite to its enantiopreference toward secondary alcohols. That is, the OH of secondary alcohols and the CH2OH of primary alcohols point in opposite directions. We suggest, however, that this opposite orientation does not imply a different position of the substituents in the active site of the lipase. Instead, PCL accommodates the extra CH2 in primary alcohols as a kink between the stereocenter and the oxygen which allows a similar position of the alcohol oxygen in both. We tried to increase the enantioselectivity of PCL toward primary alcohols by increasing the difference in the size of the substituents but did not find a consistent increase in enantioselectivity. We suggest that high enantioselectivity toward primary alcohols requires not only a significant difference in the size of the substituents, but also control of the conformation along the C(l)-C(2) bond.