Introduction: Data on temporal and gender differences in referral patterns and clinical characteristics of patients referred for myocardial scintigraphy for suspected coronary artery disease (CAD), is lacking. Furthermore, the differential impact of COVID-19 pandemic on gender differences in referrals and clinical risk profile of referred patients is not known. Methods: This is a cross-sectional observational single center study of patients evaluated across 3 yearly time intervals in 2000, 2010 and 2020. We evaluated 2,615 patients (68% women) with mean age 65.9 years, who were referred for stress/rest myocardial scintigraphy. Trends in clinical characteristics and test results were compared in women and men across these intervals. Results: Men were more likely to be referred for testing than women, however there was a consistent increase in proportion of women referred over time, including the time of COVID pandemic in 2020. Men were more likely to present with typical symptoms, compared to women. Among women, there is a significant increase in prevalence of active smoking and a decrease in age at presentation and hypertension, over time (p<0.05). Among men, there was a significant decrease in history of previous MI, with no change in other risk factors over time. Across time intervals, in both men and women, there was a significant increase in EF (Ejection Fraction) and decrease in presence of ischemic myocardium at risk, identified by semi-quantitative scores including summed rest score (SRS), summed stress score (SSS) at rest (p<0.05). Conclusions: There are gender differences in proportion of men and women who are referred for stress testing, for evaluation of stable CAD. There was a substantial change in risk of inducible myocardial ischemia among male and female patients with known or suspected CAD. Our findings are relevant to understand the implications of gender differences on risk assessment and diagnostic accuracy in known or suspected CAD, over time.