BACKGROUND: The diagnostic and prognostic value of unexpected positive intraoperative cultures remains unclear in diagnosing prosthetic joint infection (PJI) in THA revisions. QUESTIONS/PURPOSES: Therefore, we asked: (1) What is the clinical importance of bacterial growth in intraoperative tissue cultures taken during first-time revision of a clinically aseptic THA in terms of all-cause rerevision and rerevision for PJI specifically? (2) Is there a difference in outpatient antibiotic treatment patterns that is dependent on the number of positive intraoperative cultures? METHODS: This register-based study included all procedures reported to the Danish Hip Arthroplasty Register (DHR) as first-time aseptic loosening revisions performed during January 2010 to May 2016. DHR data were merged with that of the Danish Microbiology Database, which contains data from all intraoperatively obtained cultures in Denmark. Both registers have been validated and have a very high degree of completeness and very few patients are missing as a result of emigration. Revisions were grouped based on the number of unexpected positive cultures growing the same bacterial genus: zero, one, or two or more cultures. We defined a positive culture as "unexpected" if it was observed after a revision THA that had been reported to the DHR as aseptic. In Denmark, cultures are routinely obtained even in revisions coded as aseptic, and in this report, 91% (2090 of 2305) of the revision THAs coded as aseptic had cultures taken. The revisions were followed until rerevision, death, or end of the 1-year followup period. The relative risk for rerevision resulting from all causes and PJI was estimated. The Danish National Prescription Registry was reviewed for outpatient antibiotic prescription within 6 weeks of revision. We included 2305 first-time aseptic revisions. Unexpected growth was found in 282 THAs (12%), of which 170 (60%) had growth in only one culture or mixed microbial growth. Coagulase-negative Staphylococcus was the dominating bacteria in 121 revisions (71%). Rerevision was performed on 163 THAs (7%) with PJI being the indication for rerevision in 43 THAs (26%). RESULTS: The risk of all-cause rerevision was greater among first-time revisions with one positive culture (relative risk [RR], 1.73; 95% confidence interval [CI], 1.07-2.80; p = 0.020), but not in the two or more positive group (RR, 1.52; 95% CI, 0.82-2.80; p = 0.180) when compared with the culture-negative THAs. First-time revisions with one positive culture also had a higher risk of rerevision for PJI specifically (RR, 2.63; 95% CI, 1.16-5.96; p = 0.020), but this was not the case in the two or more positive group (RR, 2.28; 95% CI, 0.81-6.43; p = 0.120). Outpatient antibiotic prescription was more frequent after revisions with two or more positive cultures compared with culture-negative revision (50 of 112 [45%] versus 353 of 2023 [17%]; p < 0.001). This was not the case in revisions with one positive culture (36 of 170 [21%] versus 353 of 2023 [17%]; p = 0.220). CONCLUSIONS: First-time clinically aseptic THA revisions with unexpected growth in one biopsy culture had an increased risk for rerevision, both in terms of all-cause revision and revision for PJI. The predominant bacteria in revisions with later rerevision was coagulase-negative Staphylococcus. This emphasizes that unexpected bacterial growth with common bacteria may be clinically important, even if only one of five biopsy cultures is positive. LEVEL OF EVIDENCE: Level III, therapeutic study.