Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen in hospitals, and increases rapidly in the community, named as community-associated MRSA (CA-MRSA). We conducted a prospective/retrospective study to understand the epidemiology, antimicrobial susceptibility, and molecular characteristics of MRSA infections in adult patients in Taiwan.From March to June, 2012, all clinical MRSA isolates were prospectively collected from adult patients in a tertiary hospital in northern Taiwan. Selective isolates were further characterized. We reviewed the detailed medical record of each case retrospectively.A total of 857 clinical isolates were collected from 555 patients. A total of 749 isolates from 453 patients were classified as healthcare-associated (HA)-MRSA and 108 isolates from 102 patients as CA-MRSA by the epidemiologic criteria. Compared to HA-MRSA, CA-MRSA isolates were significantly more frequently identified from pus (78% vs 28%, P < 0.001) and less frequently from sputum (4.6% vs 43.8%, P < 0.001) and blood (3.7% vs 15%, P = 0.002). CA-MRSA isolates were more susceptible to all antibiotics tested. A total of 102 CA-MRSA and 101 HA-MRSA isolates were characterized, showing significantly different molecular characteristics between CA and HA isolates (P < 0.001). The clone of sequence type (ST) 59/t437 complex, with 2 pulsotypes, accounted for 70% of CA isolates. Three major clones were identified from HA-MRSA isolates, namely clonal complex (CC) 59 (32.7%), CC239 (29.7%), and CC5 (24.8%). Among HA isolates, a significant difference was also seen between community-onset and hospital-onset MRSA isolates in terms of the source of specimens, antibiotic susceptibility patterns, and molecular characteristics.CA-MRSA isolates from adults in northern Taiwan were genetically significantly different from HA isolates. The community clones, CC59, spread into hospitals.