The efforts for a broad application of the appropriate use criteria to reduce inappropriate nuclear stress testing have frequently been unsuccessful and the reported rates of inappropriateness have varied widely between studies. We sought to analyze the criteria of clinical appropriateness of a cohort of consecutive patients referred to our nuclear cardiology laboratory to perform stress myocardial perfusion imaging (MPI) and to assess the relationships between test appropriateness and the evaluation of ischaemia. A cohort of 251 consecutive patients, admitted to our Institute from January to March 2015, who underwent stress/rest MPI on a dedicated cardiac camera equipped with cadmium–zinc–telluride detectors, was selected. The level of clinical appropriateness of each MPI test was categorized in each patient according to the AUC criteria. According to the accepted criteria, the majority of the MPI stress-tests could be classified as clinically appropriate (218 of 251, 87 % of the tests), while only 16 (6 %) and 17 (7 %) resulted of uncertain appropriateness or clearly inappropriate, respectively. Of the 251 appropriate tests, 22 (10 %), 65 (30 %), and 131 (60 %) showed the presence of a mild (SDS < 4), moderate (4 ≥ SDS < 7), and severe (SDS ≥ 7) ischemic burden, respectively, while none of the inappropriate test showed moderate-to-severe ischaemia (P < 0.001 for comparisons). The rate of inappropriate MPI tests is considerably low in a high-volume laboratory. Appropriate and inappropriate studies identify patients at high and low probability of significant ischemia, respectively, providing insights on the effects of the level of appropriateness on stress-test results.