Background Several treatments for plaque psoriasis are available, but it remains challenging for physicians to make informed treatment decisions due to a lack of head-to-head trials. Objectives This network meta-analysis (NMA) compares the efficacy of brodalumab to other biologic agents in Canada for moderate-to-severe plaque psoriasis. Methods A systematic literature review of randomized controlled trials (RCTs) published before October 2017 was conducted to populate the NMA. Comparators included etanercept, infliximab, adalimumab, ustekinumab, secukinumab, ixekizumab, guselkumab, and placebo. The primary outcome was the psoriasis area and severity index (PASI) response at the end of induction phase. A random effects Bayesian multinomial likelihood and probit link model analyzed PASI 75, 90, and 100 responses. Inconsistency and heterogeneity were assessed. Sensitivity analyses were conducted to explore potential effect modifiers like baseline PASI score, age, and weight. Results A total of 43 RCTs were included. Brodalumab 210 mg had significantly better PASI response than etanercept, ustekinumab, adalimumab, secukinumab, and guselkumab and comparable responses to infliximab and ixekizumab. Relative risk of PASI 90 response for brodalumab varied from 2.84 (95% credible interval [CrI]: 2.35-3.52, P < .05) to 0.99 (95% CrI: 0.88-1.11, ns) compared to etanercept and ixekizumab. This was similar across PASI 75 responses, but a larger relative risk between brodalumab and all comparators except ixekizumab was observed for PASI 100. No significant heterogeneity or inconsistencies were identified. The results were consistent across sensitivity analyses, indicating robustness of the results. Conclusion Brodalumab 210 mg has efficacy superior to most biologic agents for moderate-to-severe plaque psoriasis in Canada.