Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non-muscle-invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta-analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette-Guerin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random-effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty-seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta-analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta-regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias.