Objective The purpose of our study was to determine whether sex affects the predictive value of perfusion and wall motion imaging obtained with real time myocardial contrast echocardiography (RTMCE) when compared with conventional stress echocardiography (CSE). Methods We prospectively enrolled 1649 age-matched men and women with intermediate pretest probability of coronary artery disease (CAD) undergoing stress echocardiography for suspicion of CAD. Patients with known CAD were excluded. Those who consented to participate in the study were randomised to undergo either CSE or RTMCE. Events were defined as death, non-fatal myocardial infarction (MI) and need for revascularisation. Results Median follow-up was 2.6 years (927 women, 722 men). Mean age was 58±13 years in both sexes. There were a total of 62 deaths, 12 MIs and 85 revascularisations with a 2-year event rate of 3.5% (95% CI 2.7% to 4.7%). Male sex was a significant independent predictor of adverse outcome (death, non-fatal MI) in both CSE and RTMCE (CSE HR 2.07, 95% CI 1.07 to 4.02, RTMCE HR 2.14; 95% CI 1.04 to 4.33). Higher 2-year event rates were noted in men in comparison with women after a normal CSE (men 5.4%, women 1.6%, p=0.02), but not after a normal RTMCE (men 5.8%, women 3.7%, p=0.41). Event rates were also significantly higher in men after an abnormal RTMCE (men 34.8%, women 16.4%, p=0.02) but no difference in outcome between sexes was observed after an abnormal CSE (men 17.8%, women 18.6%, p=0.90). Conclusions The addition of perfusion imaging with RTMCE improves the predictive value of stress echocardiography in men with no known CAD, but does not improve the predictive value in age-matched women.