Background Elective switching between anti-tumour necrosis factor (TNF) agents not necessarily dictated by efficacy or tolerability occurs in clinical practice. A study was undertaken to evaluate prospectively the impact of elective switching of patients with Crohn's disease well controlled with intravenous infliximab to subcutaneous adalimumab in a controlled trial. Methods An open-label randomised single-centre trial recruited 73 patients with ongoing response to at least 6 months of scheduled maintenance infliximab. Patients were randomised to continue intravenous 5 mg/kg infliximab or to switch to subcutaneous adalimumab 80 mg at baseline followed by 40 mg every other week for 1 year. Dose optimisation was allowed for intermittent flares, and patients with loss of response or intolerance could cross over to the alternative treatment group. Tolerability, patient preference and efficacy of both treatment options were the primary outcomes. Results Dose optimisation or interruption of treatment occurred in 17/36 patients (47%) in the adalimumab group and in 6/37 patients (16%) in the infliximab group (p=0.006). One patient interrupted infliximab treatment and 10 patients interrupted adalimumab treatment (p=0.003), mostly for loss of tolerance. Overall, patients preferred adalimumab treatment. All five serious adverse events were related to complicated Crohn's disease and occurred in patients randomised to adalimumab. Injection site reactions were more frequent than infusion reactions (8 vs 1, p=0.01), but only the latter caused cessation of further dosing. Anti-TNF serum levels were stable throughout the 1-year period in both groups. Conclusion Elective switching from infliximab to adalimumab is associated with loss of tolerance and loss of efficacy within 1 year. Adherence to the first anti-TNF agent is recommended.