Medication review and supply by pharmacists involves both cognitive and technical skills related to the safety and appropriateness of prescribed medicines. The cognitive ability of pharmacists to recall, synthesise and memorise information is a critical aspect of safe and optimal medicines use, yet few studies have investigated the clinical reasoning and decision-making processes pharmacists use when supplying prescribed medicines. The objective of this study was to examine the patterns and processes of pharmacists’ clinical reasoning and to identify the information sources used, when making decisions about the safety and appropriateness of prescribed medicines. Ten community pharmacists participated in a simulation in which they were required to review a prescription and make decisions about the safety and appropriateness of supplying the prescribed medicines to the patient, whilst at the same time thinking aloud about the tasks required. Following the simulation each pharmacist was asked a series of questions to prompt retrospective thinking aloud using video-stimulated recall. The simulated consultation and retrospective interview were recorded and transcribed for thematic analysis. All of the pharmacists made a safe and appropriate supply of two prescribed medicines to the simulated patient. Qualitative analysis identified seven core thinking processes used during the supply process: considering prescription in context, retrieving information, identifying medication-related issues, processing information, collaborative planning, decision making and reflection; and align closely with other health professionals. The insights from this study have implications for enhancing awareness of decision making processes in pharmacy practice and informing teaching and assessment approaches in medication supply.