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Focus on patient section. • Two vaccines are licensed in the US and Canada to prevent shingles in ≥50-year-olds. • We compare the efficacy, reactogenicity, and safety of these vaccines (ZVL and RZV). • The short term reactogenicity of RZV was higher than that of ZVL. • Both vaccines have comparable safety profiles. • The vaccine efficacy (VE) of RZV was greater than the VE of ZVL in ≥60-year-olds. We estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials. A systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age. RZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VE RZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VE ZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VE RZV = 0.91 (95%CI: 0.87, 0.94), VE ZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VE RZV = 0.89 (95%CI: 0.70, 0.96), VE ZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VE RZV = 0.89 (95%CI: 0.69, 0.96), VE ZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs. RZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL. [ABSTRACT FROM AUTHOR]