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Negative culture result is frequently encountered in periprosthetic joint infection, but its clinical feature has not been well studied. In this study, clinical characteristics and treatment outcome were compared in two patient groups: (1) 40 periprosthetic joint infections with negative culture results (culture-negative group) and (2) 135 patients with positive culture results (culture-positive group). In comparison of two groups, the culture-negative group showed significantly higher incidence of prior antibiotic use (p = 0.005), higher incidence of prior resection surgery (p < 0.001) and lower ESR (p = 0.02) than the culture-positive group. The success rate of infection control was higher in the culture-negative group (p = 0.006), which suggests that culture negativity may not necessarily be a negative prognostic factor for periprosthetic joint infection.