Torchia MT, et al. - Culture-based techniques were compared with next-generation sequencing (NGS) regarding cost-effectiveness in diagnosing periprosthetic joint infection (PJI) after total knee arthroplasty. Using a Markov, state-transition model projecting lifetime costs and quality-adjusted life years (QALYs), researchers did not identify culture as cost-effective compared to NGS, with an incremental cost-effectiveness ratio of $422,784 per QALY. The pretest probability of PJI and the performance characteristics of the NGS technology primarily influence the cost-effectiveness of NGS to diagnose PJI. In line with the existing knowledge, results support reserving NGS for clinical contexts with a high pretest probability of PJI.