Background: Cardiometabolic health typically declines with age and is worse among individuals living with obesity. Weight loss medications have modified the potential for weight loss across the life course, but it remains unclear whether weight reduction in later midlife contributes to improved cardiometabolic health, or if continuing to gain weight may continue to worsen cardiometabolic health. Methods: Using the nationally representative 1958 National Child Development Study (NCDS), a British birth cohort, associations were examined using lagged linear regression between weight change between ages 50-55 and health outcomes at age 62 (n=6,309 high-density lipoprotein (HDLc) and low-density lipoprotein (LDLc) cholesterol, systolic and diastolic blood pressure (SBP and DBP), heart rate, triglycerides, C-reactive protein (CRP), and glycated haemoglobin (HbA1c). Models accounted for prior biomarker levels at age 44. We also explored impacts of weight change on subsequent body composition. Results: Those who gained weight into or within obesity had less favourable cardiometabolic profiles and experienced faster deterioration of cardiometabolic markers between the ages of 44 and 62 than those remaining in healthy weight (e.g. SBP: 5.726, 95% CI: 2.660 to 8.793, p < 0.001; CRP: 0.802, 95% CI: 0.409 to 1.196, p < 0.001). Those who lost weight from obesity had similar rates of cardiometabolic biomarker deterioration to the healthy weight group (SBP: 0.947, 95%CI: -6.605 to 8.499, p=0.806; CRP: 0.140, 95% CI: -0.774 to 1.055, p= 0.764). Conclusion: Weight change in midlife tends towards increasing obesity and associated adverse cardiometabolic risk. Those who lose weight experienced improved cardiometabolic profiles. By viewing midlife as a modifiable stage of the life course, this study highlights opportunities to promote cardiometabolic health, and limit the speed of health decline.