Objective This study was designed to discover the relationship between bacteremia and the presence of specific bacterial species in the synovial fluid of the human temporomandibular joint (TMJ). Study design Sixteen volunteers (female to male, 1:2.2; average age, 30.00 +/- 9.93 years) who received operations via intraoral incision participated in this study. Samples from the blood and TMJ synovial fluid of the patients were taken preoperatively and postoperatively and analyzed by PCR assays with specific primers for the clinically important bacteria Staphylococcus aureus , Streptococcus mitis , and beta-hemolytic Streptococcus . Results PCR-based assays revealed the occurrence of S aureus in 68.8% and 50% of the total blood and synovial fluid samples collected immediately after the operations, which statistically differed from the preoperative samples ( P < .05). However, the frequency of the other bacteria, S mitis and beta-hemolytic Streptococcus , in pre- and postoperative blood samples had no such a difference ( P > .05). The chi-square test showed a significant association between the presence of S aureus in the blood and in TMJ synovial fluid (chi 2 = 6.409, P < .05), and the probability of hematogenous infection of the TMJ was estimated as 55.5%. Conclusion Hence, the data obtained provided evidence that the invasion of S aureus into TMJ synovial fluid was due to the presence of these bacteria in the blood. To our knowledge, this is the first report of the bacteremia-related mechanism of S aureus invasion in the human TMJ.