Objectives: To examine the variation in patient’s health outcomes across different type, route, and strength of menopausal hormone therapy (HT). Design: Retrospective case-control study Setting: United States 2007-2020 Population: 10 million women aged 65 or more in US Medicare. Methods: Cox regression models with time-varying type, route, and strength of HT as well as patient characteristics. Main Outcome(s): all-cause mortality; 5 cancers- breast, lung, endometrial, colorectal, ovarian cancers; 6 CV conditions- ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, acute myocardial infarction; and dementia. Results Estrogen monotherapy (ET) exhibited a significant, 19% (HR=0.81; 95% CI 0.79-0.82), relative risk reduction on mortality. The reduction was greater with estradiol and vaginal/transdermal than conjugated estrogen and oral preparations. ET also exhibited significant risk reductions for all study cancers; breast (15%), lung (13%), endometrial (29%), colorectal (13%) and ovarian (14%). All ET preparations except low-dose slightly increased risk of ischemic heart diseases (1-4%). Both combination therapy and progestogen monotherapy exhibited significantly increased risk of breast cancer (7-14%). Oral ET exhibited moderately increased risk of stroke (6%) and dementia (2%). Conclusions: Among senior Medicare women, the effect of menopausal HT varies by type, route, and strength. The use of estradiol, vaginal/transdermal, and low/medium for menopausal care is safer than its counterparts.