Abstract : Erythema nodosum leprosum (ENL) is an acute inflammatory reaction in multibacillary (MB) type leprosy patients which is the main cause of disability. Several studies support theory that antibody levels of MB patients with ENL are higher than those without ENL. Therefore, this study was conducted to determine the difference between anti-PGL-1 immunoglobulin titers in MB type leprosy patients with and without ENL reactions. Analytical observational study with prospective cohort design was conducted to test the IgM and IgG titer levels of MB type leprosy patients who had ENL reaction and those who had not. Data analysis compared immunoglobulin titers between the two study groups using independent t-test. From 20 samples obtained, 12 of them were MB type leprosy patients with ENL reactions, while 8 others were without ENL. Anti PGL-1 IgM levels in MB group with ENL reactions were significantly higher than those in MB group without ENL reactions (1.081±0.386 vs. 0.401±0.212; p<0.001). Likewise, anti-PGL-1 IgG levels were significantly higher with a comparison of 0.713±0.216 vs. 0.354±0.202; p=0.002. High formation of antigen- antibody complexes as a response to humoral immunity is apparently not able to kill pathogens, but is carried in the circulation and settles on skin, triggering an ENL reaction in MB leprosy patients. The levels of anti-PGL-1 IgM and IgG in MB group with ENL reaction were significantly higher than those in MB group without ENL reaction.