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Backgroud Influenza viruses cause substantial morbidity, especially in older age groups. Thus, they are amongst high priority groups for routine vaccination. However, vaccine-induced immune responses and effectiveness were reported as relatively low. This study aims to systemically compare the immune responses elicited by intramuscular (IM) and intradermal (ID) injections with inactivated seasonal influenza vaccine among the older age group. Methods A prospective, open-label, randomized study with a total of 221 adults (>60 years) were enrolled and randomized into 2 groups. Group I (n = 111) received an IM inactivated seasonal influenza vaccine while Group II (n = 110) received the same vaccine ID. Demographics and co-morbidity were collected at baseline. Safety data was collected 3 days post-vaccination using diary card. HAI, NAb and NAI titers were assessed prior to vaccination and at 30, 45, and 60 days post-vaccination. Data was analyzed using SPSS 11.5. Results Both groups had similar BMI and co-morbidity. For ID and IM groups, significant differences were observed for seroconversion rate measured using HAI against H1N1 and H3N2 (58/111 vs 44/110 and 68/111 vs 54/110, respectively) being higher for those aged 60–65 years. However, no differences in HI antibody against B/Phuket were seen. For ID route, history of hyperlipidemia and hypertension were factors associated with high seroconversion rate towards influenza A (p = .001). The seroconversion rate risk ratio were 1.31 and 1.25 (p < .05) against A/California/07/09(H1N1) and A/Songkha/308/13 (H3N2), respectively. Interestingly, the GMT (95% CI) of baseline NAI antibodies among both groups were high (56.57 and 54.01 in the ID and IM groups, respectively). A 4-fold increase measured by NAI against A/California/07/09 (H1N1) were detected in 16.67% and 20% of participants who received ID or IM vaccination, respectively. Conclusions The seroconversion rates of HAI, NAb and NAI were modest, especially in those >65 years of age. However, it was higher in the ID group as compared to the IM group. Clinical trial registration: NCT02101749 [ABSTRACT FROM AUTHOR]