One hundred and eighty eight organisms were isolated from clinical specimens (71 isolates from urine, throat swabs (40), stool (39) pus (17), blood (14), wound swabs (7) collected from laboratories of hospitals and polyclinics distributed in Najran Area, Saudi Arabia, between February 2010 to November 2011. Bacteria were identified by Gram staining and biochemical tests, and antibiotic sensitivities tested by the disc diffusion method at microbiology laboratory, NajranUniversity. The most prevalent bacteria isolated were E. coli (35.63%) followed by Klebsiella pneumoniae (18.08%), Staph. aureus (14.89%), Salmonella spp. (13.29%), Pseudomonas aeruginosa (6.91%), Streptococcus pneumoniae (5.31%), Shigella spp (3.19%), Enterococcus faecalis (1.59%) and Proteus mirabilis (1.06%). The multi-drug resistance rates (MDR) among common isolates were Pseudomonas aeruginosa (38.46%) followed by Klebsiella pneumoniae (32.35%), Staph. Aureus (32.14%) and E. coli (31.34%). The overall multi-drug resistance rate among isolates was high (28.72%).