The prognostic value of dobutamine stress echocardiography (DSE) for risk stratification of patients aged ≥ 80 years is not clearly defined. A follow-up of 3 ± 2 years for major cardiac events and all-cause mortality was obtained in 227 patients, age ≥ 80 years, who underwent DSE for known or suspected coronary artery disease. Stress function index (SFI), calculated as the ratio of peak wall motion score index to left ventricular ejection fraction, was analyzed both as continuous variable and categorized using the mean value of 5 as the cut-off. Only 95 patients (42%) of this group underwent a cycloergometer exercise stress test (EST). During DSE 118 patients developed inducible ischemia; SFI was 4.9 ± 2.6 and 60 subjects showed a value higher than 5. EST gave a positive result in 12 patients and a negative result in 8 patients; it was inconclusive for inadequate increase in heart rate in 75 (79%) subjects. Advanced age (HR: 1.184/year, 95% CI: 1.073-1.306, p = 0.001) and SFI ≥ 5 (HR: 2.682, 95% CI: 1.429-5.035, p = 0.002) were independent predictors of all-cause mortality; advanced age (HR: 1.252/year, 95% CI: 1.064-1.473, p = 0.007), SFI ≥ 5 (HR: 3.181, 95% CI: 1.174-8.621, p = 0.02) and presence of left bundle branch block (HR: 3.060, 95% CI: 1.057-8.862, p = 0.039) independently predicted an increased occurrence of major cardiac events. No parameter derived from EST showed an independent prognostic role. DSE showed a significant prognostic value in octogenarians, both for all-cause mortality and major cardiac events.