OBJECTIVES: To investigate patterns of early repeat prescriptions and treatment switching over an 11-year period to estimate differences in the cost of medication wastage, dispensing fees and prescriber time for short (<60 days) and long (≥60 days) prescription lengths from the perspective of the National Health Service in the UK. SETTING: Retrospective, multiple cohort study of primary care prescriptions from the Clinical Practice Research Datalink. PARTICIPANTS: Five random samples of 50 000 patients each prescribed oral drugs for (1) glucose control in type 2 diabetes mellitus (T2DM); (2) hypertension in T2DM; (3) statins (lipid management) in T2DM; (4) secondary prevention of myocardial infarction; and (5) depression. PRIMARY AND SECONDARY OUTCOME MEASURES: The volume of medication wastage from early repeat prescriptions and three other types of treatment switches was quantified and costed. Dispensing fees and prescriber time were also determined. Total unnecessary costs (TUC; cost of medication wastage, dispensing fees and prescriber time) associated with <60 day and ≥60 day prescriptions, standardised to a 120-day period, were then compared. RESULTS: Longer prescription lengths were associated with more medication waste per prescription. However, when including dispensing fees and prescriber time, longer prescription lengths resulted in lower TUC. This finding was consistent across all five cohorts. Savings ranged from £8.38 to £12.06 per prescription per 120 days if a single long prescription was issued instead of multiple short prescriptions. Prescriber time costs accounted for the largest component of TUC. CONCLUSIONS: Shorter prescription lengths could potentially reduce medication wastage, but they may also increase dispensing fees and/or the time burden of issuing prescriptions.