Guselkumab is a fully human immunoglobulin-G1-lambda (IgG1λ) monoclonal antibody that binds selectively to the p19 subunit of interleukin 23. Few series of real clinical practice that reflect the use of guselkumab have been published so far, including the measure of survival at more than 52 weeks. An observational, longitudinal, retrospective study of real clinical practice of patients with moderate to severe psoriasis receiving treatment with guselkumab 100 mg subcutaneous every 8 weeks in five tertiary hospitals in Andalusia (Spain) was carried out. A total of 87 patients were included in this study. Disease severity and treatment response was assessed by PASI, BSA, VAS pruritus, and DLQI at baseline and after 4, 12, 24, 36, 52, and 76 weeks. Data are presented as mean ± SD for continuous variables, and number and percentage for categorical variables. To determine the differences between visits in PASI, BSA, VAS pruritus, and DLQI a Wilcoxon matched-pairs test was performed. The survival of guselkumab was calculated using Kaplan-Meier survival analysis. Our population presented with a mean age of 49.9 years, 60.9% of them were male, had a mean PSO evolution of 20.4 (9.5) years. A total of 79.3% were obese or presented with overweight and had several comorbidities (dyslipidemia 28.7%, arterial hypertension 23% and 20% diabetes among others). At baseline their disease parameters were: PASI = 14.6 (7.2), BSA = 22.3 (16.6), VAS pruritus = 6.0 (2), and DLQI = 15.8 (5). After 52 weeks their disease improved to PASI = 0.9 (1.1), BSA = 1.0 (1.8), VAS pruritus = 0.47 (0.88), and DLQI = 1.54 (2.50). The percentage of patients who achieved PASI 75, 90, and 100 at 52 weeks was 90.3%, 71%, and 51.6%, respectively. The patients evaluated at week 76 (n = 3) reached PASI 0, BSA 0, and DLQI 0. After 93.4 weeks (1 year, 9 months, and 14 days), the overall survival rate was 94% (4 events were reported). A total of four patients discontinue to AE or lack of efficacy after 76 weeks. Guselkumab showed excellent results in the control of psoriasis in the mid-term with an elevated number of patients maintaining treatment after 52 to 76 weeks and a good safety profile.