The aim of this study is to evaluate the effect of different levels of realism of context learning on the prescribing competencies of medical students during the clinical clerkship in internal medicine. Between 2001 and 2007, 164 medical students took part in the prospective explorative study during their clinical clerkship in internal medicine at the VU University Medical Center, Amsterdam, The Netherlands. In a fixed order, each student had to formulate a treatment plan for a real patient in three situations of increasing realism: a minimal level (studying a patient record), medium level (preparing for a therapeutic consultation), and optimal level (preparing for and performing a therapeutic consultation with the patient). In comparison to studying a patient record (minimal context level), preparing a therapeutic consultation (medium context) improved four of the six steps of the WHO six-step plan. Preparing and performing a therapeutic consultation with a real patient (optimal context) further improved three essential prescribing competencies, namely checking for contraindications and interactions, prescription writing, and instructions to the patient. The results of this first explorative study suggest that enrichment of the learning context (responsibility for patient care) might be an important factor to improve the training of rational prescribing skills of medical students during their clinical clerkship in internal medicine. Clinical (pharmacology) teachers should be aware that seemingly small adaptations in the learning context of prescribing training during clinical clerkships (i.e., with or without involvement with and responsibility for patient care) may have relatively large impact on the development of prescribing competencies of our future doctors.