We aimed to investigate the immune responses to homologous and heterologous COVID-19 booster vaccinations in renal transplant recipients (RTRs) and to identify factors affecting these responses. In this prospective multicenter observational study, we measured the antibody kinetics of 90 RTRs using the chemiluminescent microparticle immunoassay method. The mean age of participants was 45.2 ± 11.4 years, with 35.6% being female. On the 42nd day after the first vaccine dose, the median antibody level was 16.7 (IQR 2.5-249.5) AU/mL, and the seropositivity rate was 60% (n = 36). Mycophenolic acid (MFA) (OR: 0.087, 95% CI: 0.024-0.311) and ACE inhibitor use (OR: 0.203, 95% CI: 0.052-0.794) were identified as independent factors affecting seropositivity. Patients who received the Pfizer/BioNTech booster had significantly higher antibody levels compared to those who received the CoronaVac/Sinovac booster (p = 0.021). Additionally, a significantly higher rate of COVID-19 positivity was observed among patients who received the CoronaVac/Sinovac booster (p = 0.031). Heterologous COVID-19 booster vaccination is significantly more effective than homologous inactivated booster vaccination in enhancing immune responses and preventing new infections in RTRs. MFA and ACE inhibitor usage were independent factors affecting seropositivity. Additional COVID-19 vaccine doses are needed in this patient group.