Summary Background. Efalizumab is approved by the European Medicines Evaluation Agency for the treatment of adult patients with moderate to severe plaque psoriasis who fail to respond to, have a contraindication for, or cannot tolerate other systemic therapies. Objectives. To evaluate the efficacy and safety of efalizumab treatment in daily practice at a dermatology department in a teaching hospital in Barcelona, Spain. Methods. A cohort study was carried out for patients treated with efalizumab for at least 3 months between May 2005 and July 2007. In total, 31 patients [21 men, 10 women; mean psoriasis and severity index (PASI) 12.9] were treated with efalizumab. Data were collected prospectively, including PASI, and recorded at the start of treatment and at follow-up visits with a frequency of at least every 3 months. Results. At the end of the study period, efalizumab treatment was ongoing in 18 of the 31 patients (58.1%), and 7 of these patients had been treated for ≥ 24 months. At week 12, 67.7% of the patients treated with efalizumab had achieved an improvement of 50% in PASI (PASI 50), 41.9% reached PASI 75, and 16.1% reached PASI 90 (intention to treat and as-treated analyses). In all, 19 patients (61.3%) received treatment for ≥ 24 weeks. At week 24, 89.5% of these patients reached PASI 75, and 26.3% reached PASI 90 (as-treated analysis). During efalizumab treatment, mainly mild adverse effects were reported, including transient papular or circinate exacerbations of psoriasis, which were seen in five patients (16.1%). Rebounds (defined as PASI ≥ 125% of baseline, leading to erythroderma in two patients) occurred in 7/31 patients (22.6%); this occurred while on treatment in 5/11 nonresponding patients (45.5%) and after discontinuation of treatment in 2/20 patients with good response (10.0%). Conclusion. Efalizumab is an effective and safe treatment for psoriasis in most patients of a high need population in routine practice, and provides maintained improvement in ‘responders’. Combination treatment was transiently used in 48.4% of patients to optimize therapeutic results. Special consideration must be given to possible rebound in patients with an inadequate response or after discontinuation of treatment.