The aim of this study was to elucidate and describe students' thinking about organic chemistry reactions of small versus large drug-like molecules. Thirty-six students enrolled in a Pharmaceutical Organic Chemistry course participated in individual, think-aloud interviews. The interview protocol included questions about five reactions with the same reagents but with starting materials of varying complexity. The interviews were inductively coded for similarities and differences in students' reasoning. Constant-comparative analysis was used to identify patterns in students' thinking. The study was designed to test the assumption that, with the increased complexity of the reactant molecules, students will find it increasingly more difficult to propose a reaction mechanism and arrive at a correct final product. Our assumption was not supported by the data; students successfully proposed the mechanism for reactions containing a ketone group, regardless of the complexity of the starting material. In contrast, many students proposed incorrect mechanisms and arrived at incorrect final products when reducing ester or carboxylic acid groups. Students successfully used the strategies that were taught in the course to simplify large drug-like molecules, which is why the complexity of the starting materials did not impact their performance. Instructors are encouraged to use these strategies to scaffold reactions of large drug-like molecules to support student sense-making. At the same time, when proposing mechanisms for molecules with certain functional groups, students displayed a tendency to rely on memorization. Students, therefore, need further support in developing mechanistic reasoning by practicing engaging in scientific argumentation supported by evidence.