<b>87</b> <h3>Objectives</h3> Recently, we confirmed diabetic foot evaluation superiority with dual isotope (DI) SPECT/CT over Tc-99m HDP bone (BS) or In-111 WBC (WBCS) SPECT/CT scans alone. In this study, we investigate if SPECT/CT use is necessary for high accuracy of DI. <h3>Methods</h3> Flow & blood pool imaging were followed by WBC reinjection & DI BS & WBCS planar (PL) & SPECT/CT acquisitions. Tc-99m sulfur colloid/In-111 WBC (step 2 DI) SPECT/CT was obtained in 8 patients (pt) with suspected mid/hindfoot osteomyelitis (OM). DI PL, SPECT & SPECT/CT were separately reviewed by 2 observers for lesion (LS) location, confidence (uncertain, certain), diagnosis (Dx) & Dx confidence based on each review. Final Dx was determined as OM, soft tissue infection (STI), combined OM/STI or other pathology by surgical/pathological &/or up to 24 months follow-up. <h3>Results</h3> Of 61 pt, 50 had confirmed Dx. Final Dx prediction by SPECT/CT was higher than SPECT or PL DI, assessed by Lambda (0.74, 0.46, 0.16) & error reduction % (70%, 45%, 23%), respectively. Of 111 LS seen by all images, Dx confidence was higher (p < 0.001) in SPECT/CT than SPECT or PL DI. Compared with SPECT/CT, LS location was incorrect in 29% SPECT & 32% PL DI. All 8 pt with Step 2 DI SPECT/CT had improved Dx, achieving a superior accuracy (Lambda 0.89, error reduction 86%), which included 1 false negative (chronic OM) & 2 false positive (1 gouty arthritis, 1 without pathology) Dx. <h3>Conclusions</h3> In DI imaging of diabetic foot, SPECT/CT considerably improves detection & discrimination of STI & OM while providing precise anatomic localization. When needed, step 2 DI SPECT/CT can yield additional information for a more definitive Dx.