Medical treatment for fistulizing Crohn's disease (FCD) is changing rapidly over the time by the introduction of novel therapeutic medicines, while no global consensus is available. This study aims to accomplish a systematic review and meta-analysis on the efficacy of tumor necrosis factor-alpha antibodies (anti-TNF-α antibodies) versus placebo in FCD. A systematic review of published literature was carried out till December 2016, and a meta-analysis of identified studies was done. Data have been explored from PubMed, Scopus, Cochrane Library Database, and Web of Science. Predefined exclusion criteria for included studies in meta-analysis are based on search methodology and are as follows: Randomized clinical trial about Crohn's disease (CD) patients without fistula, pediatrics CD, randomized clinical trials about pregnant women with FCD, nonhuman studies, randomized clinical trials with surgical therapies interventions, conference abstracts, case reports, and language other than English studies. All randomized placebo-controlled trials were included. To assess risk of bias, Jadad score was applied to evaluate trials' methodological quality. Relative risk (RR) and 95% confidence intervals were computed using Mantel-Haenszel and/or Rothman-Boice (for fixed effects) or Der Simonian-Laird (for random effects) techniques. Nine studies attained defined inclusion criteria. The meta-analysis results showed that anti-TNF-α antibodies are remarkably more effective in comparison to placebo for fistula closure maintenance (RR = 2.36; 95% confidence interval: 1.58–3.55; P < 0.0001) in patients with FCD, whereas anti-TNF-α antibodies were not superior to placebo neither in fistula improvement nor in fistula closure. We concluded that adalimumab and certolizumab pegol are both effective in fistula closure maintenance in adult patients with FCD.