The purpose of this study is to evaluate the prognostic value of myocardial perfusion SPECT obtained in CZT cameras (CZT–SPECT) with multipinhole collimation in obese patients. CZT–SPECT may be technically challenging in the obese, and its prognostic value remains largely unknown. Patients underwent single-day, rest/stress (supine and prone) imaging. Images were visually inspected and graded as poor, fair or good/excellent. Summed stress and difference scores (SSS and SDS, respectively) were converted into percentages of total perfusion defect and of ischemic defect by division by the maximum possible score. Obesity was defined as a body mass index (BMI) ≥ 30 kg/m² and classified as class I (BMI 30–34.9 kg/m²), II (BMI 35–39.9 kg/m²), or III (BMI ≥ 40 kg/m²). Patients were followed-up by telephone interview for the occurrence of all-cause death, myocardial infarction or revascularization. A Cox proportional hazards analysis was used to assess the independent predictors of death. Among 1396 patients, 365 (26.1 %) were obese (mean BMI 33.9 ± 3.6; 17.5 % class I, 3.4 % class II, and 3.4 % class III). Image quality was good/excellent in 94.5 % of the obese patients. The annualized mortality rates were not significantly different among obese and non-obese patients, being <1 % with normal CZT–SPECT, and increased with the degree of scan abnormality in both obese and non-obese patients. Age, the use of pharmacologic stress and an abnormal CZT–SPECT, but not obesity, were independent predictors of death. In obese patients, single-day rest/stress CZT–SPECT with a multipinhole camera provides prognostic discrimination with high image quality.