The molecular and crystal structures of 19 N‐alkyl‐substituted pipecolamide derivatives with partial fluorination of N‐propyl and N‐butyl groups are presented. Fluorination patterns include one F‐atom at internal or terminal locations, two F‐atoms in geminal or vicinal arrangements at various positions, as well as terminal trifluoromethylation. Due to the presence of the carboxamide side chain in pipecolamide derivatives, enantiomeric fluorination patterns in the N‐alkyl group result in diastereomeric compounds, which exhibit dramatically different crystal and molecular structures. An extraordinary conformational diversity is diagnosed for the various N‐alkylpiperidine units. Structural comparisons and theoretical assessments based on extensive force field calculations provide insight into consistent conformational patterns that point to intramolecular factors as well as intermolecular modulations due to crystal packing effects. [ABSTRACT FROM AUTHOR]