Background : Indonesia is a country with high tuberculosis (TB) cases in this world. In the 2015 there are 60% new cases and 10% of them happened in children. This is the reason why BCG immunization must given in 0-3 months of life and under the universal immunization programme. The effectiveness of BCG immunization can be seen by the appereance of local BCG responses. However, local BCG response can be influenced by the immune system. In infants with low birth weight (LBW) are easier to get infected by bacteria or other microorganism because of the immune system is not as perfect as infants with normal birth weight (NBW). The purpose of this study is to analyze the difference of the local BCG response in LBW and NBW. Methods : This study used an observational study and a prospective cohort study design. Respondents this study were babies with low birth weight (LBW) and normal birth weight (NBW) and they have been given BCG immunization between December 2017 until June 2018 at the RS PKU Muhammadiyah Yogyakarta or RS PKU Muhammadiyah Gamping. Respondents have to complete the inclusion and exclusion criteria. Every respondent who complete the criteria will be followed for 12 weeks or until the local BCG response appear every two weeks. The sampling method used consecutive sampling. Data analyzed used chi-square test and logistic regression. Results : In this study, 80 respondents were involved. They are 40 respondents in LBW group and 40 resondents in NBW group. Local BCG response was found in the LBW group (70.0%), which is lower than NBW group (95.0%) and it is significant (p = 0.003, RR = 6.000, 95% CI 1.434-25.106). Beside that, other factors that can affect the result of local BCG responses were found in this study such as gestational age (56.2% premature and 100% premature) and age of immunization (1 month 97.2% and 2 month 70.5%). That results show a significantly different in the incidence of local BCG responses. Conclusion : In conclusion the proportion of local BCG responses in LBW and NBW groups is significantly different. There are other factors that have different of local BCG response such as gestational age and immunization age.