The objective of this study was to determine the changing trend of leptospirosis over time in Thailand using two prospective hospital-based studies conducted amongst adult patients with acute undifferentiated fever (AUFI) admitted to Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima Province, Thailand between July 2001 to December 2002 and between July 2011 to December 2012. During the first period, leptospirosis (98 patients, 40%) and scrub typhus (59 patients, 24.1%) were the two major causes of AUFI. In the second period, scrub typhus (137 patients, 28.3%) was found to be more common than leptospirosis (61 patients, 12.7%). Amongst patients with leptospirosis, the proportion of male patients and the median age were similar. Leptospira interrogans serogroup Autumnalis was the major infecting serogroup in both study periods. The case fatality rate of leptospirosis was significantly higher in 2011-2012 as compared with the case fatality rate in 2001-2002 (19.7% vs. 6.3%, p < 0.001). In summary, we found that number of leptospirosis cases had decreased over time. This trend is similar to reportable data for leptospirosis complied from passive surveillance by the Ministry of Public Health, Thailand. However, the case fatality rate of severe leptospirosis has increased. Severe lung hemorrhage associated with leptospirosis remained the major cause of death.