OBJECTIVES: To compare and contrast the Medication Possession Ratio (MPR) and Proportion of Days Covered (PDC) measures of adherence and explore the implications of measure choice and specific definition on study results. METHODS: Two adherence measures, MPR and PDC, were selected for comparison because of their prominence in the claims database research literature. To highlight the effect of measure selection, examples demonstrating contrasting results for MPR and PDC are presented. Furthermore, the impact of numerator and denominator specification within each of those measures is examined and illustrated with examples. Implications for assessing and interpreting published research studies are presented. RESULTS: Although MPR and PDC have been operationally defined in similar ways in the literature, there are differences that could yield distinct results. The basic structure of these measures is a ratio with a proxy for the number of compliant days in the numerator and the number of days in a measurement period in the denominator. MPR is based on the sum of dispensed ‘days supply’ over a period, whereas PDC is based on evaluation of available supply for each individual day in the period. A demonstration is provided on how research design choices of MPR or PDC and specification of numerator and denominator can result in different findings for a given research question.  CONCLUSIONS: Despite the similar structure of MPR and PDC metrics, study design choices can affect study results considerably. Selection of an adherence measure must be tailored to the therapeutic area, relevant medications, and research objectives. Researchers should be transparent in the specification of measures used and readers need to understand the implication of these research design decisions.