BACKGROUND: The preoperative differentiation of aseptic and septic loosening of hip prostheses remains a diagnostic challenge for clinicians and many molecular imaging techniques have been evaluated. The objective of current study was to establish the clinical utility of dual phase 18F-fluoride PET/CT (DPFP) in diagnosing implant loosening, differentiation between septic and aseptic loosening and to compare the diagnostic accuracy of DPFP and three-phase bone scan (TPBS). METHODS: In this prospective study, we evaluated 57 hip components in 45 patients (bilateral prostheses in 12 patients, 45 painful and 12 asymptomatic contralateral hip components) with dual phase fluoride PET/CT and TPBS. Findings of skeletal scintigraphy and PET/CT were evaluated by two expert nuclear medicine physicians, blinded with clinical findings and final diagnosis. The patterns of tracer uptake and maximum standardized uptake value (SUVmax) were noted for each joint. The final diagnosis was based on intraoperative findings, histopathological or microbiological examinations. RESULTS: Out of twelve non-painful hips, DPFP correctly identified no loosening in 11 hips while TPBS detected in 10 hips. In the remaining 45 hips with radiological proven loosening to rule out sepsis, DPFP had a sensitivity, specificity, PPV, NPV and accuracy of 75%, 97%, 92%, 88% and 88% respectively while TPBS revealed 81%, 86%, 76%, 89% and 82% respectively. DPFP had shown a higher specificity and PPV as compared to the TPBS in the evaluation of painful hip prostheses. The pattern of tracer uptake may help in the differentiation between the two entities. We also noted a significant difference between SUVmax values of septic and aseptic loosening. CONCLUSIONS: The results suggested that DPFP has considerable potential in differentiating septic from aseptic loosening of hip prostheses and more specific to rule out sepsis than TPBS. It may be employed before revision arthroplasty to evaluate implant for loosening and sepsis in loosened implant.