Real-world evidence (RWE) meta-analyses provide valuable insights from patients in routine clinical practice. Secukinumab, the first fully human monoclonal antibody that neutralizes IL-17A, has shown long-lasting effectiveness and safety in plaque psoriasis (PsO). Since its license approval in 2015, many RWE studies have been published. The objective of this study was to review all available literature on RWE studies with secukinumab and the secukinumab arm of comparator studies in patients with moderate-to-severe PsO to evaluate its effectiveness, drug survival, and safety. https://www.embase.com and https://clinicaltrials.gov databases were searched using prespecified inclusion criteria between 1 January 2015 and 31 May 2019. Using a meta-package and R statistical software to analyze data, key outcomes were measured at 3, 6, and 12 months. PASI and DLQI score data were recorded for patients who remained on secukinumab treatment. Overall, 43 studies were included. Drug survival was 90% at 3 and 6 months, and 80% at 12 months. At 12 months, 8% of patients had discontinued treatment due to lack of effectiveness. At 3, 6, and 12 months, Psoriasis Area and Severity Index (PASI) 90 scores were as follows: 50%, 53%, and 60%, and PASI 100 scores were 36%, 46%, and 51%, respectively. At 3, 6, and 12 months, 57%, 55%, and 65% of patients achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, respectively. Adverse events were consistent with rates observed in clinical trials with no new safety signals. This meta-analysis strengthens existing evidence on the clinical effectiveness of secukinumab in patients with moderate-to-severe PsO, demonstrating high drug survival rates, high levels of patient-reported outcomes, and good tolerance.