Invasive diseases consist of pneumonia, meningitis and sepsis are generally caused by Streptococcus pneumoniae (S. pneumoniae). The disease incidence always increases every year with high mortality and morbidity rates, as well as the increased economic burden. The purpose of this study was to determine the total cost of illness (COI) for invasive diseases treatment, and to compare direct medical costs with INA-CBG's tariff in accordance with the Permenkes RI No.64/2016 on pediatric inpatient in Dr. Sardjito Yogyakarta. This research is a descriptive research using an observational method with cross sectional design according to the prospective societal and provider. This research is conducted prospectively on September 2017-February 2018 by interviewing using questionnaires, as well as tracking data document data in the ICM section, guarantee and accounting. The comparison of direct medical cost with INA-CBG's tariff used statistical test methods namely Independent t-test and Mann-Whitney. Data obtained ware 52 patient with pneumonia, 8 patients with meningitis and 4 patients with sepsis. Total of COI obtained were Rp2.215.867.036, with the direct medical costs as the largest component. The comparison of direct medical cost with INA-CBG's tariff result showed J-4-16-I code has 6 pneumonia patients, 7 patients with J-4-16-II code, 8 patients with J-4-16-III code, 3 meningitis patients with code G-4-19-II, 1 patient with G-4-19-III code, and 2 sepsis patients with A-4-10-III code. Data that met the test criteria, obtained p value 0.240 for J-4-16-I code, and p value 0.305 for J-4-16-II code, which indicates that there is no significant difference between real cost and INA-CBG's. While the results of p value 0.04 for J-4-16-III code and p value 0.037 G-4-19-II code, indicates significant differences between the two. With average the overall patients direct medical cost is greater than INA-CBG's tariff.