The diagnosis of cardiac transthyretin amyloidosis can involve early or delayed99mTc-pyrophosphate planar, single photon emission computed tomography (SPECT), and/or SPECT/CT imaging. We investigated whether image interpretations differed among modalities and time points. In this observational study, data were reviewed for 173 patients with suspected transthyretin amyloidosis who underwent planar and SPECT/CT 1 and 3 hours after radiopharmaceutical injection. Planar heart-to-contralateral lung ratios were calculated. Myocardial-to-rib uptake was independently scored on SPECT and SPECT/CT as follows: 0 (negative), 1 < rib (equivocal), 2 = rib (positive), or 3 > rib (positive), and the image quality was as follows:1 (poor), 2 (adequate), and 3 (good). Three-hour SPECT/CT readings were used as the reference standard against which the other readings were compared. Twenty-five percent of patients were positive (3-hour SPECT/CT score ≥ 2). Compared to 3-hour SPECT/CT readings, there was “fair agreement” (κ= .27 − .33) with SPECT, and “fair agreement” (κ= .23 − .31) with planar imaging at 1 and 3 hours. More patients had abnormal SPECT and SPECT/CT than planar imaging (24–25% vs 16–17%,P< .007). There were more equivocal cases for 1 and 3 hours planar imaging than for 1 and 3 hours SPECT (71–73% vs 23–26%,P< .001) and 1 and 3 hours SPECT/CT (3–5%,P< .001). SPECT/CT image quality was higher at 3 hours than at 1 hour and higher than that on SPECT (P= .001). Three-hour SPECT/CT readings provided the highest number of definitive readings, had the highest image quality, and constituted the preferred protocol for evaluating unselected populations of patients that have a clinical suspicion of possible cardiac amyloidosis.