Background: The booster vaccination for Covid-19 prevention has been specifically recommended among high-risk populations such as older people. Previous studies have reported that intradermal (ID) vaccination could be as effective as intramuscular (IM) or subcutaneous (SC) vaccination In addition, ID vaccination causes less systemic adverse effects which are much concerned by older people giving rise to lower vaccination rate in this particular age group. Therefore, this study aims to compare the immunogenicity and adverse effects following ID and IM booster vaccination of mRNA vaccines against COVID-19 in older populations. Methods: This randomized, open-label study was conducted at a single center, Siriraj Hospital, Bangkok, Thailand, which was completed in July 2022. The eligible participants were individuals aged 65 years or older who already had received 2-dose IM primary series of ChAdOx1 vaccine within 12-24 weeks. Participant were randomly assigned to six vaccine groups: ID mRNA-1273 (20 mcg; 0.1 ml, n=35), IM mRNA-1273 (100 mcg; 0.5 ml, n=35), ID BNT162b2 (10 mcg; 0.1 ml, n=35 for each group of 65-79 and ≥ 80 years of age) and IM BNT162b2 (30 mcg; 0.3 ml, n=35 for each group of 65-79 and ≥ 80 years of age). Self-reported adverse events (AEs) were collected for 7 days consecutively following each vaccination using an electronic diary application. The immunogenicity was determined by the level of IgG antibodies against receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S1 subunit). The pseudotype-based neutralization assays (PVNT) were used to measure neutralizing antibodies against SARS-CoV-2 variants. The T-cell response was measured using S-peptide and NMO-peptide stimulation. Results: Of 210 participants, the majority (70.5%) were female, median age was 77.5 years old (Interquartile range (IQR): 71.0-84.0 years old). At 4 weeks after booster vaccination, the geometric mean concentration (GMC) of anti-RBD IgG increased in all groups by overall of 45.11 (95% CI: 38.82, 52.41) folds from baseline. The GMC among participants who received IM mRNA-1273 had gained the highest immunogenic responses and significantly higher than IM BNT162b2 (GMC of IM mRNA-1273: 3,837.12 BAU/mL, GMC of IM BNT162b2: 2,530.58 BAU/mL, p=0.021). ID vaccination had significantly lower GMC than IM of the same vaccine type. Across vaccine groups, the geometric mean titer against Omicron variant BA.1 was the highest among participants who received IM mRNA-1273 boosting (616.8), followed by ID mRNA-1273 (213.9), IM BNT162b2 (144.6), and ID BNT162b2 (82.1). The ID route had significantly more frequent local AEs than IM with the highest rate among ID mRNA-1273 and the lowest in ID BNT162b2 group. Conclusion: The IM mRNA-1273 group gained the highest immunogenic responses as well as experienced less systemic AEs than BNT162b2. Although ID route achieved lower level of antibody than IM route, the immunologic responses were highly enough to create vaccine efficacy and caused less systemic AEs. Therefore, the ID mRNA-1273 could be the alternative type of Covid-19 vaccination for older people.