Streptococcus pneumoniae was isolated from 170 patient specimens at Siriraj Hospital during January-December 2008. Patients were 66% male and ranged in age from 3 months to 94 years (mean +/- SD = 38.2 +/- 31.7). The largest proportion (29.4%) of isolates were from patients older than 60 years, followed by patients aged 2-5 years (20%) and from patients less than 2 years (12.4%). Monthly isolation was highest in December (22 isolates in December compared to the average of 13 isolates of the other months). Antimicrobial susceptibility for eight drugs was determined by the disk diffusion method. Overall, susceptibility was generally high to chloramphenicol (71.8%), linezolid (100%), ofloxacin (93.5%) and vancomycin (100%), but less susceptible to erythromycin (35.3%), penicillin (31.1%), tetracycline (28.8%) and trimethoprim/ sulfamethoxazole (24.1%). Among the 105 (62%) isolates resistant to three or more drugs, the most common resistance pattern was erythromycin-penicillin-tetracycline-trimethoprim/sulfamethoxazole, accounting for 39% of such isolates, followed by chloramphenicol-erythromycin-penicillin-tetracycline- trimethoprim/sulfamethoxazole (29.5%). The minimal inhibitory concentrations (MIC) of penicillin and cefotaxime were determined by broth microdilution. By 2008 CLSI criteria, 92% and 90% of 51 sterile site isolates were penicillin and cefotaxime susceptible, including one of two meningitis cases. In contrast, of 26 non-sterile site isolates, only 26.9% and 76.9% were susceptible to penicillin and cefotaxime, respectively. The MICs of penicillin were higher for isolates from non-sterile sites than for those from sterile sites.