Background Evidence is required on the clinical effectiveness and cost-effectiveness of emergency surgery compared with non-emergency surgery strategies (including medical management, non-surgical procedures and elective surgery) for patients admitted to hospital with common acute gastrointestinal conditions. Objectives We aimed to evaluate the relative (1) clinical effectiveness of two strategies (i.e. emergency surgery vs. non-emergency surgery strategies) for five common acute conditions presenting as emergency admissions; (2) cost-effectiveness for five common acute conditions presenting as emergency admissions; and (3) clinical effectiveness and cost-effectiveness of the alternative strategies for specific patient subgroups. Methods The records of adults admitted as emergencies with acute appendicitis, cholelithiasis, diverticular disease, abdominal wall hernia or intestinal obstruction to 175 acute hospitals in England between 1 April 2010 and 31 December 2019 were extracted from Hospital Episode Statistics and linked to mortality data from the Office for National Statistics. Eligibility was determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis codes, which were agreed by clinical panel consensus. Patients having emergency surgery were identified from Office of Population Censuses and Surveys procedure codes. The study addressed the potential for unmeasured confounding with an instrumental variable design. The instrumental variable was each hospital’s propensity to use emergency surgery compared with non-emergency surgery strategies. The primary outcome was the ‘number of days alive and out of hospital’ at 90 days. We reported the relative effectiveness of the alternative strategies overall, and for prespecified subgroups (i.e. age, number of comorbidities and frailty level). The cost-effectiveness analyses used resource use and mortality from the linked data to derive estimates of incremental costs, quality-adjusted life-years and incremental net monetary benefits at 1 year. Results Cohort sizes were as follows: 268,144 admissions with appendicitis, 240,977 admissions with cholelithiasis, 138,869 admissions with diverticular disease, 106,432 admissions with a hernia and 133,073 admissions with an intestinal obstruction. Overall, at 1 year, the average number of days alive and out of hospitals at 90 days, costs and quality-adjusted life-years were similar following either strategy, after adjusting for confounding. For each of the five conditions, overall, the 95% confidence intervals (CIs) around the incremental net monetary benefit estimates all included zero. For patients with severe frailty, emergency surgery led to a reduced number of days alive and out of hospital and was not cost-effective compared with non-emergency surgery, with incremental net monetary benefit estimates of –£18,727 (95% CI –£23,900 to –£13,600) for appendicitis, –£7700 (95% CI –£13,000 to –£2370) for cholelithiasis, –£9230 (95% CI –£24,300 to £5860) for diverticular disease, –£16,600 (95% CI –£21,100 to –£12,000) for hernias and –£19,300 (95% CI –£25,600 to –£13,000) for intestinal obstructions. For patients who were ‘fit’, emergency surgery was relatively cost-effective, with estimated incremental net monetary benefit estimates of £5180 (95% CI £684 to £9680) for diverticular disease, £2040 (95% CI £996 to £3090) for hernias, £7850 (95% CI £5020 to £10,700) for intestinal obstructions, £369 (95% CI –£728 to £1460) for appendicitis and £718 (95% CI £294 to £1140) for cholelithiasis. Public and patient involvement translation workshop participants emphasised that these findings should be made widely available to inform future decisions about surgery. Limitations The instrumental variable approach did not eliminate the risk of confounding, and the acute hospital perspective excluded costs to other providers. Conclusions Neither strategy was more cost-effective overall. For patients with severe frailty, non-emergency surgery strategies were relatively cost-effective. For patients who were fit, emergency surgery was more cost-effective. Future work For patients with multiple long-term conditions, further research is required to assess the benefits and costs of emergency surgery. Study registration This study is registered as reviewregistry784. Funding This project was funded by the National Institute for Health and Care Research (IHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 1. See the NIHR Journals Library website for further project information.