BACKGROUND: Soft liners (SLs) are easily colonized and infected by Candida species and bacteria, leading to denture-induced stomatitis. Hence, it is essential that the SLs be taken care of. To serve such a purpose, antimicrobial zeolites have been incorporated. Limited in vitro evidence suggests that silver zeolite (SZ) is a potentially effective antimicrobial agent. Hence, this study aims to analyze and compare the antimicrobial effectiveness of SZ when added to two different types of SLs in vivo for 28 days in complete denture patients. MATERIALS AND METHODS: This study was undertaken to determine the efficacy of SZ as an antimicrobial agent when incorporated in acrylic soft liners (ASLs) and silicone soft liners (SSLs). A total of 32 edentulous patients were selected and were divided into two groups. Group 1 consisted of 16 patients, wherein SSL was used, and Group 2 consisted of 16 patients with ASL. The reduction of colony-forming units (CFUs) was seen in both the groups after an interval of 28 days. RESULTS: There was a greater reduction noted when SZ was incorporated in SSLs after 28 days. Group 1 showed a mean reduction of CFU from 4.60 to 1.98, whereas Group 2 showed a mean reduction from 4.73 to 3.39. Thus, SZ was effective in both the SLs. CONCLUSION: SZ showed a significant reduction in CFU in both the SLs. Hence, this in vivo study concluded that incorporation of SZ is effective as an antimicrobial agent when added to SLs.