The objective of the study was to evaluate the pattern of antibiotic resistance of Streptococcus pneumoniae at Saudi Aramco Medical Services Organization (SAMSO) in the Eastern Province of Saudi Arabia. We identified, retrospectively, S. pneumoniae isolates from January 1999 to December 2002. Antimicrobial susceptibility and clinical data were collected and analyzed. A total of 162 isolates of S. pneumoniae were identified in the study period. Of these isolates, 94 (58%) isolates were obtained from out-patients and 68 (42%) were obtained from in-patients. Thirty-five percent of isolates were from blood, 46% from the respiratory tract, and the remainder were obtained from other sites. Of these isolates, 83 (51%) were penicillin-susceptible and the remaining 79 (48.8%) were not penicillin susceptible. High-level resistance to penicillin existed in 19.8% of the total isolates. Prevalence of resistance to erythromycin, tetracycline and trimethoprim-sulfamethoxazole was 25%, 29%, and 42% respectively. None of the isolates was resistant to vancomycin or ceftriaxone. However, 12% of the isolates showed multi-drug resistance. Streptococcus pneumoniae shows 19.8% high-level penicillin resistance and 12% multi-drug resistance. These findings call for wiser use of antibiotics.