Background To summarize the current evidence on the effects of intra-arterial chemotherapy (IAC) on high-risk non-muscle invasive bladder cancer (NMIBC) and compare oncology results with intravesical chemotherapy (IVC). Methods We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest by a systematical search of multiple scientific databases in February 2021. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous variables respectively, with 95% confidence intervals (CIs). The hazard radio (HR) with 95% CIs was used for overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS). Results A total of six studies with 866 patients were included. For IAC combined with IVC versus IVC alone, statistically significant differences were found regarding tumor recurrence rate (OR: 0.51, 95% CI [0.36~0.72], p=0.0001), tumor progression rate (OR: 0.47, 95% CI [0.30~0.72], p=0.0006), tumor-specific death rate (OR: 0.49, 95% CI [0.25~0.99], p=0.05), PFS (HR: 0.47, 95% CI [0.23~0.96], p=0.04) and RFS (HR: 0.60, 95% CI [0.41~0.87], p=0.007). No significant difference between two groups was found for time to first recurrence (MD: 3.27, 95% CI [-2.37~8.92], p=0.26) and OS (HR: 1.20, 95% CI [0.44~3.32], p=0.72). For IAC alone versus IVC, There was no statistical difference in the terms of tumor-specific death rate (OR: 0.67, 95% CI [0.29~1.53], p=0.34), RFS (HR: 0.90, 95% CI [0.56~1.46], p=0.68) and PFS (HR: 0.71, 95% CI [0.32~1.55], p=0.39). Adverse events mainly included nausea/vomiting (36.3%), hypoleukemia (19.4%), neutropenia (16.0%), increased creatinine (9.9%), increased alanine aminotransferase (18.7%), and thrombocytopenia (9.9%). Conclusion The IAC combined with IVC is a safe and effective treatment for high risk NMIBC, with lower rates of recurrence, progression, tumor-specific death, PFS and RFS, and with minor and tolerable events. The effectiveness of the IAC alone is parallel to the IVC alone.