Objectives: Cardiac implantable electronic device (CIED) infection has been a major clinical problem in addition to being a major financial burden. In spite of antimicrobial prophylaxis, CIED infection rates have been increasing disproportionately. We therefore conducted this meta-analysis to assess the role of TYRX antibiotic envelope for the prevention of CIED infection. Methods: Using extensive online search, we conducted a meta-analysis of studies reporting CIED infections with versus without the use of TYRX antibiotic envelope. A random-effect model was used, and between studies heterogeneity was estimated with I 2. All analyses were performed with RevMan (version 5.0.20). Results: Five cohort studies were included in this meta-analysis. The pooled odds ratio (OR) of included studies was 0.29 [95% confidence interval (CI): 0.09-0.94; p < 0.004]. There was evidence of heterogeneity with I 2 of 58%. There was also evidence of publication bias on funnel plot analysis. On sensitivity analysis, no statistically significant difference was noted when stratified by study design or duration of follow-up. Conclusion: The results of our study demonstrate a significant beneficial effect of TYRX antibiotic envelope for the prevention of CIED infections.