Background Ligelizumab, a next‐generation, humanized anti‐immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard‐of‐care therapy. Objective To evaluate the long‐term safety and re‐treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods This open‐label, single‐arm, long‐term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose‐finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post‐treatment for 48 weeks. Results Overall, ligelizumab was well‐tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment‐emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks. Conclusion The long‐term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re‐treatment efficacy was shown. Trial Registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218. A total of 226 patients received ligelizumab 240 mg for 52 weeks. Overall, 84.1% of patients experienced at least one TEAE. After 52 weeks of treatment, 53.1% of patients had a complete response and 75.8% of patients had cumulative complete responses. The long‐term safety profile of ligelizumab 240 mg in patients was consistent with the core study and re‐treatment efficacy was shown.Abbreviations: BAS, basophil; CSU, chronic spontaneous urticaria; FcεRI, Fc epsilon receptor 1; IgE, immunoglobulin E; MC, mast cell; MoA, mechanism of action; TEAE, treatment‐emergent adverse event; UAS7, weekly urticaria activity score; UAS7 = 0, complete response; UAS7 ≤ 6, minimal disease activity