Objectives: In this study, we tried to evaluate pandemic H1N1(pH1N1) natural infection effect on immunogenicity of following inactivated influenza vaccination containing A/California/7/2009 (H1N1)-like strain. Subjects and methods: From October 2010 to May 2011, we conducted an observational open label prospective multi-center study to assess the immunity of seasonal influenza vaccine containing A/California/7/2009 (H1N1)-like strain and its long-term persistence after vaccination in children and adolescents ranged from 6 months to 18 years. The study was performed at five hospitals located in Seoul and Gyeonggi-do, Korea. The children who identified by history of seasonal influenza vaccine and pH1N1 vaccine in 2009-2010 seasons were classified as pH1N1 vaccine primed subjects (VP group: 109 subjects) and pH1N1 infection primed subjects (IP group: 21 subjects). The history of pH1N1 natural infection in 2009-2010 seasons was also identified with history taking and questionnaire. We measured antibody titers with a haemagglutination-inhibition assay at baseline , 30 days, and 6 months after 1st or 2nd flu shot depending on his or her past influenza vaccine history. VP group and IP group were compared with immunogenicity and long term immunity. Immunogenicity and long term immunity were expressed as the percentage of subjects with HI antibody ≥1: 40, seroconversion rate, and geometric mean titers. Results: The percentage of subjects with HI antibody ≥1: 40 in VP group at baseline, post vaccination 1 month, 6 month was 54.98%, 75.33%, 58.88% and in IP group 54.55%, 75.76%, 73.08% respectively. There was no difference of seroprotection rate between two groups. In comparison of seroconversion rate, VP group and IP group showed 36.80% and 66.67% respectively. IP group showed better seroconversion rate than VP group. In comparison of geometric mean titer (GMT), GMT in VP group at baseline, post vaccination 1 month, 6 month was 27.65, 66.22, 37.28 and in IP group 27.40, 160.00, 61.28 respectively. IP group showed better long term immunity than VP group for those GMT at 6 month post vaccination. Conclusion: Conclusively, it is supposed that p-H1N1 natural infection has superior effects to p-H1N1 vaccination on immunogenicity and long term immunity of following inactivated influenza vaccination containing A/California/7/2009 (H1N1)-like strain.