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Objective. Acute and chronic calcium pyrophosphate (CPP) crystal arthritis is characterized by the presence of synovial CPP crystals within a clinically inflamed joint. CPP crystals may be situated intracellularly or extracellularly; however, the clinical significance of their location remains understudied. The objective of this retrospective cohort study was to assess the relevance of the CPP crystal location in diagnosing acute/chronic CPP crystal arthritis. Methods. Data were collected from Waikato District Health Board to identify a study population with synovial fluid samples positive for CPP crystals. The cohort was stratified into 2 groups based on crystal location: intracellular and extracellular. The proportions of acute/chronic CPP crystal arthritis cases were compared between these groups. Acute/chronic CPP crystal arthritis was diagnosed when synovial CPP crystals were present, with objective evidence of joint inflammation and no other alternative diagnosis. Further analysis was made with respect to demographics, other laboratory results, and cartilage calcification. Results. This study included 134 patients: 108 with intracellular CPP crystals and 26 with extracellular CPP crystals. Acute/chronic CPP crystal arthritis was diagnosed in 85% of cases in the intracellular and 50% in the extracellular group (P < 0.001). Following exclusion of septic arthritis cases, acute/chronic CPP crystal arthritis was diagnosed in 97% of patients in the intracellular group and in 62% of those in the extracellular group (P < 0.001). Conclusion. The presence of intracellular CPP crystals is more strongly associated with acute/chronic CPP crystal arthritis than with extracellular CPP crystals alone. [ABSTRACT FROM AUTHOR]