BACKGROUND: The proportion of days covered (PDC) is used to estimate medication adherence by looking at the proportion of days in which a person has access to the medication, over a given period of interest. This study aimed to adapt the PDC algorithm to allow for plausible assumptions about prescription refill behaviour when applied to data from online pharmacy suppliers. METHODS: Three PDC algorithms, the conventional approach (PDC1) and two alternative approaches (PDC2 and PDC3), were used to estimate adherence in a real-world dataset from an online pharmacy. Each algorithm has different denominators and increasing levels of complexity. PDC1, the conventional approach, is the total number of days between first dispensation and a defined end date. PDC2 counts the days until the end of supply date. PDC3 removes from the denominator specifically defined large gaps between refills, which could indicate legitimate reasons for treatment discontinuation. The distribution of the three PDCs across four different follow-up lengths was compared. RESULTS: The dataset included people taking ACE inhibitors (n = 65,905), statins (n = 100,362), and/or thyroid hormones (n = 30,637). The proportion of people taking ACE inhibitors with PDC ≥ 0.8 was 50-74% for PDC1, 81-91% for PDC2, and 86-100% for PDC3 with values depending on drug and length of follow-up. Similar ranges were identified in people taking statins and thyroid hormones. CONCLUSION: These algorithms enable researchers and healthcare providers to assess pharmacy services and individual levels of adherence in real-world databases, particularly in settings where people may switch between different suppliers of medicines, meaning an individual supplier's data may show temporary but legitimate gaps in access to medication. Accurately identifying problems with adherence provides the foundation for opportunities to improve experience, adherence and outcomes and to reduce medicines wastage. Research with people taking medications and prescribers is required to validate the algorithms' assumptions.