Introduction: Typhoid fever is a common disease in Yunnan province; however, the resistant phenotype and epidemic characteristics of Salmonella in this area are still unclear. In this study, a 15-year surveillance of antimicrobial susceptibility of Salmonella is reported. Methodology: From January 1999 to December 2013, Salmonella isolates were recovered from patients in the First People's Hospital of Yunnan Province. Antimicrobial susceptibility was detected and data were analyzed using WHONET5.6. Results: A total of 845 Salmonella isolates were recovered between 1999 and 2013. The most frequently isolated Salmonella serovar was S. Paratyphi A (93%), and 75.1% (635/845) of the isolates were from the young and middle-aged population. The resistance rates of Salmonella spp. to ciprofloxacin, ampicillin, and ceftriaxone increased dramatically during the 15 years. Carbapenems retained the highest and most stable activity against isolates. The resistance rates of all Salmonella isolates to chloramphenicol and sulfamethoxazole were 0.4% (3/845) and 1.8% (15/845), respectively. Conclusions: As Salmonella isolates have been observed to be resistant to first-line antibiotics, antimicrobial agents should be used rationally and prescriptions should be based on case-by-case susceptibility testing.