Melioidosis, caused byBurkholderia pseudomallei, is a notifiable disease associated with a high mortality rate in Thailand. The disease is highly endemic in northeast Thailand, while its prevalence in other parts of the country is poorly documented. This study aimed at improving the surveillance system for melioidosis in southern Thailand, where the disease was believed to be underreported. Two adjacent southern provinces, Songkhla and Phatthalung, were selected as the model provinces to study melioidosis. There were 473 individuals diagnosed with culture-confirmed melioidosis by clinical microbiology laboratories at four tertiary care hospitals in both provinces from January 2014 to December 2020. The median age was 54 years (IQR 41.5–64), 284 (60%) of the patients were adults ≥50 years of age, and 337 (71.2%) were male. We retrospectively analyzed 455 patients treated at either Songklanarind Hospital, Hatyai Hospital, Songkhla Provincial Hospital, or Phatthalung Provincial Hospital, of whom 181 (39.8%) patients died. The median duration from admission to death was five days (IQR 2–17). Of the 455 patients, 272 (57.5%) had at least one clinical risk factor, and 188 (39.8%) had diabetes. Two major clinical manifestations, bacteremia and pneumonia, occurred in 274 (58.1%) and 166 (35.2%) patients, respectively. In most cases, 298 (75%) out of 395 local patients were associated with rainfall. Over the seven years of the study, the average annual incidence was 2.87 cases per 100,000 population (95% CI, 2.10 to 3.64). This study has confirmed that these two provinces of southern Thailand are endemic to melioidosis; even though the incidence rate is much lower than that of the Northeast, the mortality rate is comparably high.