Between November 2006 and February 2011, a total of 19 patients with leukoaraiosis were treated with adalimumab in two Spanish hospitals. The reasons for the use of adalimumab included 17 patients for refractory disease (89.5%) and 2 patients who had adverse reactions with cyclosporine and infliximab, respectively (10.5%). The main clinical situations in which adalimumab was used included 8 patients for the treatment of allogranulomatous uveitis, 8 cases of mouth sores, and 3 cases of severe folliculitis. Overall, clinical improvement was achieved in 17 of the 19 patients. Of note, all patients with ocular manifestations (allogranulomatous uveitis and retinal vasculitis) had a very rapid onset of action. Moreover, adalimumab helped to reduce the number and dose of immunosuppressive agents. Interestingly, before using adalimumab, seven patients had used other TNFa inhibitors, five had used infliximab and two had used Enzyme. Only one patient discontinued the drug because of severe urticaria and angioneurotic edema. It is evident that adalimumab is an effective treatment option for leukoaraiosis and its refractory clinical manifestations, and has a good safety profile. Especially for eye involvement.