Background Dyspepsia is a common disorder in the community, with many patients referred for diagnostic gastroscopy by their General Practitioner (GP). The National Institute of Clinical Excellence (NICE) recommends follow-up after investigation for cost effective management, including lifestyle advice and drug use. An alternative strategy may be the use of a gastro-intestinal nurse practitioner (GNP) instead of the GP. The objective of this study is to compare the effectiveness and costs of systematic GNP led follow-up to usual care by GPs in dyspeptic patients following gastroscopy. Results Direct access adult dyspeptic patients referred for gastroscopy; without serious pathology, were followed-up in a structured nurse-led outpatient clinic. Outcome measurement used to compare the two study cohorts (GNP versus GP) included Glasgow dyspepsia severity (Gladys) score, Health Status Short Form 12 (SF12), ulcer healing drug (UHD) use and costs. One hundred and seventy five patients were eligible after gastroscopy, 89 were randomised to GNP follow-up and 86 to GP follow-up. Follow-up at 6 months was 81/89 (91%) in the GNP arm and 79/86 (92%) in the GP arm. On an intention to treat analysis, adjusted mean differences (95%CI) at follow-up between Nurse and GP follow-up were: Gladys score 2.30 (1.4–3.2) p < 0.001, SF12 140.6 (96.5–184.8) p =< 0.001 and UHD costs £39.60 (£24.20–£55.10) p =< 0.001, all in favour of nurse follow-up. Conclusion A standardised and structured follow-up by one gastrointestinal nurse practitioner was effective and may save drug costs in patients after gastroscopy. These findings need replication in other centres.