Background: Streptococcus pneumoniae is significant cause of serious bacterial infections among both children and adults. These bacterial infections are most commonly community acquired pneumonia, meningitis, otitis media, endocarditis, osteomyelitis, pericarditis, pyogenic arthritis, soft tissue infection, neonatal septicemia, lower respiratory infection and bacteremia in human; all over the world, especially in developing countries. Among deaths due to lower respiratory infections in people of all age groups in 2016, S. pneumoniae contributed for 50% deaths than all other bacterial pathogens. Objective: - The aim of this study is to determine the nasopharyngeal carriage rate of Streptococcus pneumoniae, its associated risk factors, and antimicrobial susceptibility among adult individuals arrested in Hawassa prison from July, 2021 to August, 2021. Methodology: A cross sectional study was conducted from July, 2021 to August, 2021 in Hawassa prison. All randomly selected voluntary adult individual were included in the study. About 330 individual participants were enrolled in this study. The nasopharyngeal swab was collected by trained laboratory technologists obtaining individuals consent. The swab specimen was inoculated onto 5% sheep blood agar within 3 hours of collection; and, this inoculated media was incubated in CO2 enriched atmosphere at 35-37°C for 18 to 24 hours. After incubation, the suspected colonies of S. pneumoniae was identified and confirmed by typical colony morphology, alpha-hemolysis, Gram staining, optochin susceptibility and bile solubility test. Antimicrobial susceptibility testing (AST) was performed using disc diffusion method according to recommendations of the Clinical and Laboratory Standards Institute (CLSI). Result: About 41 (12.7%) of the adult individuals were colonized by S. pneumonia. The carriage rate of S. pneumoniae was affected by age classes that 39-48 years (OR=4.82, 95% CI=1.49-15.56, P=0.009), 49-58 years (OR=5.27, 95% CI=1.27-21.89, P=0.022), & greater than 58 years (OR=4.36, 95% CI=1.13-16.90, P=0.033,) cigarette smoking (OR=3.41, 95% CI=1.16-10.01, P=0.026), and sharing beds (OR=3.91, 95% CI=1.27-12.07, P=0.033). The majority of the isolates predominantly susceptible for clindamycin (85.4%) and resistance for chloramphenicol (56%). Multi drug resistance was observed in 36.7%.