Objective: This study was undertaken to determine the serotype distribution and drug susceptibility patterns in pneumococcal isolates recovered from patients with invasive pneumococcal disease (IPD). Methods: All invasive pneumococcal isolates received between June 2014 and June 2016 were included in the study as part of a national laboratory-based IPD surveillance program. Isolates recovered from clinical specimens of normally sterile body sites were included. Results: A total of 41 different serotypes were identified among the 132 pneumococcal isolates included in this study. The most prevalent serotypes/serogroups were 12 (8.3%), 15 (8.3%), 19 F (7.6%), 3 (6.1%), and 19A (6.1%);. It was observed that overall vaccine coverage rates for pneumococcal conjugate vaccines (PCV), PCV7, PCV10 and PCV13 were 15.9%, 24.2% and 37.1% respectively. 56.8% (n = 75) of the isolates were non-susceptible to at least one antibiotic and 40.9% (n = 54) of the isolates were resistant to PEN (M). 18.9% (n = 25) of the isolates were multi-drug resistant (MDR).The case fatality rate was 15.9%. Conclusion: Our study results call for broader vaccine coverage, emphasizes the need to introduce the conjugate pneumococcal vaccine for the high risk adult population and stress the importance of continuous surveillance of serotypes and antimicrobial resistance to guide vaccine development and antimicrobial stewardship activities. Keywords: Streptococcus pneumoniae, IPD, Serotype, Antibiotic resistance, Oman, Vaccination