Objectives: The purpose of this research was to study the effect of one cup of coffee taken 1 h before adenosine stress on the results of myocardial perfusion imaging. Background: Caffeine is believed to attenuate the coronary hyperemic response to adenosine by competitive blockade of the A2a receptor. Caffeine is commonly withheld before adenosine single-photon emission computed tomography (SPECT) perfusion imaging so as not to mask ischemia detection. Methods: We studied the effect of one 8-oz cup of coffee taken 1 h before adenosine stress in patients who had demonstrable reversible defects on adenosine SPECT perfusion imaging performed while off caffeine. Results: There were 22 men and 8 women, age 64 ± 9 years. The blood level of caffeine 1 h after intake was 3.1 ± 1.6 mg/l. There were two patients with ST-segment depression before and one after caffeine intake (p = NS). The summed stress score (SSS) based on 17 segments (scale of 0 to 3, 3 being normal) was 44 ± 5 before and 45 ± 5 after caffeine (p = NS). The summed difference score was 3.8 ± 1.9 before and. 3.9 ± 2.3 after caffeine (p = NS), reflecting that around 50% of the perfusion abnormality was reversible before and after caffeine. Using polar maps, the perfusion abnormality was 12 ± 10% at baseline and 12 ± 10% after caffeine (p = NS) in agreement with SSS. The left ventricular ejection fraction by gated SPECT was 50 ± 13% at baseline and 51 ± 13 % after caffeine (p = NS). Conclusions: A cup of coffee does not mask the presence or severity of reversible defects induced by adenosine SPECT imaging. © 2006 American College of Cardiology Foundation.