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Background The prevalence of non-communicable diseases, and associated morbidity and mortality, is increasing rapidly in low and middle-income countries where health systems often have limited access and lower quality of care. The intervention was to decentralise uncomplicated non-communicable disease (NCD) care from a hospital to nurse practitioners in health centres in a poor rural district in Eswatini, southern Africa. The objective of this study was to assess the feasibility and impact of decentralised care for NCDs within nurse-led clinics in order improve access and inform healthcare planning in Eswatini and similar settings. Methods In collaboration with the Eswatini Ministry of Health, we developed and implemented a package of interventions to support nurse-led delivery of care, including: clinical desk-guide for hypertension and diabetes, training modules, treatment cards and registries and patient leaflets. Ten community clinics in the Lubombo Region of Eswatini were randomly selected to be trained to deliver NCD care for a period of 18 months. Observational data on follow-up rates, blood pressure (BP), glucose etc. were recorded and evaluated. We compared blood pressure and blood glucose measurements between the first and fourth visits and fitted a linear mixed effects model. Results One thousand one hundred twenty-five patients were recruited to the study. Of these patients, 573 attended for at least 4 appointments. There was a significant reduction in mean BP among hypertensive patients after four visits of 9.9 mmHg systolic and 4.7 mmHg diastolic (p = 0.01), and a non-significant reduction in fasting blood glucose among diabetic patients of 1.2 mmol/l (p = 0.2). Key components of NCD care were completed consistently by nurses throughout the intervention period, including a trend towards patients progressing from monotherapy to dual therapy in accordance with prescribing guidelines. Conclusions The findings suggest that management of diabetes and hypertension care in a rural district setting can be safely delivered by nurses in community clinics according to a shared care protocol. Improved access is likely to lead to improved patient compliance with treatment.