BACKGROUND: Long-term conditions place a substantial burden on primary care services, with drug therapy being a core aspect of clinical management. However, the ideal frequency for issuing repeat prescriptions for these medications is unknown. AIM: To examine the impact of longer-duration (2-4 months) versus shorter-duration (28-day) prescriptions. DESIGN AND SETTING: Systematic review of primary care studies. METHOD: Scientific and grey literature databases were searched from inception until 21 October 2015. Eligible studies were randomised controlled trials and observational studies that examined longer prescriptions (2-4 months) compared with shorter prescriptions (28 days) in patients with stable, chronic conditions being treated in primary care. Outcomes of interest were: health outcomes, adverse events, medication adherence, medication wastage, professional administration time, pharmacists' time and/or costs, patient experience, and patient out-of-pocket costs. RESULTS: From a search total of 24 876 records across all databases, 13 studies were eligible for review. Evidence of moderate quality from nine studies suggested that longer prescriptions are associated with increased medication adherence. Evidence from six studies suggested that longer prescriptions may increase medication waste, but results were not always statistically significant and were of very low quality. No eligible studies were identified that measured any of the other outcomes of interest, including health outcomes and adverse events. CONCLUSION: There is insufficient evidence relating to the overall impact of differing prescription lengths on clinical and health service outcomes, although studies do suggest medication adherence may improve with longer prescriptions. UK recommendations to provide shorter prescriptions are not substantiated by the current evidence base.