60 CHAPTER 2.2 Abstract Introduction Appropriate prescribing in older people continues to be challenging. Studies still report a high prevalence of inappropriate prescribing in older people. To reduce the problem of under- and overprescribing in this population, explicit drug optimization tools like STOPP/START have been developed. The aim of this quality appraisal study was to evaluate the clinical applicability of STOPP/START criteria in daily patient care by assessing the clarity of singular criteria. Methods For each of the 114 STOPP/START criteria version 2, elements describing the action (what/how to do), condition (when to do) and explanation (why to do) were identified. Next, the clarity of these three elements was quantified on a 7-point Likert scale using tools provided by the Appraisal of Guidelines for Research & Evaluation (AGREE) Consortium. The primary outcome measure was the clarity rating per element, categorized into high (>67.7%), moderate (33.3-67.7%) or low (<33.3%). Secondary, factors that positively or negatively affected clarity most were identified. Additionally, the nature of the conditions were further classified into five descriptive components: disease, sign, symptom, laboratory finding and medication. Results STOPP recommendations had an average clarity rating of 65%, 60% and 67% for actions, conditions and explanations, respectively. The average clarity rating in START recommendations was 60% and 57% for actions and conditions, respectively. There were no statements present to substantiate the prescription of potential omissions for the 34 START criteria. Conclusion Our results show that the clarity of the STOPP/START criteria can be improved. For future development of explicit drug optimization tools, such as STOPP/START, our findings identified facilitators (high clarity) and barriers (low clarity) that can be used to improve the clarity of clinical practice guidelines (CPGs) on a language level and therefore enhance clinical applicability.