This randomized, double-blind, phase IV study (NCT05731115) assessed the lot-to-lot consistency, immunogenicity, and safety of three manufacturing lots of a 23-valent pneumococcal polysaccharide vaccine (PPV23) in 1800 healthy Chinese adults aged 40-65 y. The participants were enrolled and randomized into three groups at a 1:1:1 ratio, with each group receiving one dose of PPV23 from one of three manufacturing lots. Blood samples were collected pre-vaccination and at 30 d post-vaccination for serotype-specific IgG antibody testing. The primary objective was to demonstrate lot-to-lot consistency via equivalence evaluation in 40-65 y old Chinese adults, assessed by geometric mean concentration (GMC) of IgG antibodies at 30 d post-vaccination. Safety data were collected for up to 30 d after vaccination. The results showed that GMC ratio 95% confidence intervals (CIs) in all 23 serotypes were within the predefined equivalence criteria of (0.5, 2). Although the incidence of adverse reactions (AR) may have varied among the three lots, the clinical impact is likely minimal, given that the vast majority (93.2%) were mild in severity. No serious adverse events (SAEs) related to vaccination were reported during the study. This study confirmed that the three manufacturing lots of PPV23 (Sinovac Biotech Co. Ltd.) demonstrated manufacturing consistency and can elicit satisfactory immune responses for all 23 serotypes and no safety concerns were identified.Trial registration: ClinicalTrial.gov identifier: NCT05731115.