The study was designed as observational retrospective analysis of the data from Slovenian Registry of patients with moderate and severe psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab from 2005 to 2015. The survival rates of biologics were compared using survival analysis, and predictors of discontinuation were evaluated using a Cox regression model. All biologics have been prescribed as a first line therapy for moderate or severe psoriasis; 650 (94.9%) adalimumab, 254 (72.0%) ustekinumab, 76 (69.7%) infliximab, 68 (67.3%) etanercept. The overall biologics survival rate was 83.2% in the first line and 79.1% in the second line treatment. Drug survival for the first and second line of therapy was significantly longer for ustekinumab than for anti-TNFα agents (p < 0.001 and p = 0.014, respectively). Loss of efficacy accounted for 63% of all treatment discontinuations. Multivariate regression analysis showed that younger patients, being on etanercept, systemic conventional co-therapy, lower BSA and higher DLQI were independent predictors for treatment discontinuation. Our data showed the real-life situation in the treatment of moderate to severe psoriasis with biologics. Since longevity of drug survival is considered as a measure of treatment success, this data represents an important information when selecting a biologic treatment for individual patient.