OBJECTIVE: To compare the incidence of systemic conditions between women who had surgical treatment for stress incontinence with mesh and without mesh. DESIGN: National cohort study. SETTING: English National Health Service. POPULATION: Women with no previous record of systemic disease who had first-time urinary incontinence surgery between 1 January 2006 and 31 December 2013, followed up to the earliest of 10 years or 31 March 2019. METHODS: Competing-risks regression was used to estimate hazard ratios (HR), adjusted for patient characteristics, with HR > 1 indicating increased incidence following mesh surgery. MAIN OUTCOME MEASURES: First postoperative admission with a record of autoimmune disease, fibromyalgia or myalgic encephalomyelitis up to 10 years following the first incontinence procedure. RESULTS: The cohort included 88 947 women who had mesh surgery and 3389 women who had non-mesh surgery. Both treatment groups were similar with respect to age, socio-economic deprivation, comorbidity and ethnicity. The 10-year cumulative incidence of autoimmune disease, fibromyalgia or myalgic encephalomyelitis was 8.1% (95% CI 7.9-8.3%) in the mesh group and 9.0% (95% CI 8.0-10.1%) in the non-mesh group (adjusted HR 0.89, 95% CI 0.79-1.01; P = 0.07). A sensitivity analysis including only autoimmune diseases as an outcome returned a similar result. CONCLUSIONS: These findings do not support claims that synthetic mesh slings cause systemic disease. TWEETABLE ABSTRACT: No evidence of increased risk of systemic conditions after stress incontinence treatment with a mesh sling.