BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) is the most common bladder cancer. Many studies have reported that intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IVC) could effectively reduce the recurrence rate of NMIBC. The purpose of this study is to assess the efficacy and safety of IAC combined with IVC for patients with high-risk NMIBC. METHODS: PubMed, Cochrane Library, Medline, Embase, Web of Science, and 4 Chinese databases will be searched for eligible studies published without language restrictions from their inception up August 31, 2019. Subgroup analysis will be mainly explored in study design, types of chemotherapy drugs, and sample size. Cochrane Collaboration Risk of bias Tool will be applied in evaluating the quality of enrolled articles. Statistical analysis will be carried out by the Stata version 14.0 software. RESULTS: The primary outcome is recurrence-free survival (RFS). The secondary outcomes include overall survival (OS), progression-free survival (PFS), adverse reactions and toxicity grade coded by common toxicity criteria for adverse events. CONCLUSION: The findings of this study will provide latest evidence to verify whether IAC combined with IVC is more effective and safer than IVC alone for patients with high-risk NMIBC. PROSPERO REGISTRATION NUMBER: CRD42019146847.