Background: Intramuscular fat is greater in African compared with European ancestry men and is now recognized as a major risk factor for cardio-metabolic diseases, independent of general obesity. However, prospective studies examining health consequences of this important ectopic fat depot are lacking, particularly in high-risk African ancestry populations. Therefore, we sought to determine if change in skeletal muscle density, a measure of intramuscular fat, predicts subsequent development of hypertension in African ancestry men. Methods: We measured at two time points calf skeletal muscle density (MD; mg/cm 3 ) using computed tomography in 1504 Afro-Caribbean men aged 40-92 years (mean, 59 years), who were recruited without regard to their health status. Hypertension was defined as having a systolic blood pressure of 140 mm Hg or greater, having a diastolic blood pressure of 90 mm Hg or greater, or taking antihypertensive medications. Logistic regression was used to estimate the association between change in MD and incident hypertension adjusting for follow-up time, baseline age and muscle density, and covariates known to be associated with hypertension and intramuscular fat (baseline body weight, body weight change, waist circumference, waist circumference change, current smoking, alcohol intake, physical activity, and baseline type 2 diabetes status). Results were expressed as the odds (95% CI) of hypertension per one standard deviation decrease in muscle density. Results: During the 6.2 years follow-up (range of follow-up years: 4.9-9.1 years), we observed a significant annualized percent decrease in muscle density (-0.43 %/yr; P<0.0001). Among the 777 men who were normotensive at the baseline visit, 224 (28.8%) developed hypertension during follow-up. Decreased MD during follow-up was associated with an increased risk of hypertension (odds ratio [95% CI] per SD decrease in MD: 1.31 [1.03, 1.67]). This association remained significant after additional adjustment for baseline waist circumference and change in waist circumference in a separate model (odds ratio [95% CI] per SD decrease in MD: 1.27 [1.02, 1.59]). Conclusions: Our novel findings show that ectopic intramuscular fat increases with advancing age, and support a causal role of intramuscular fat in hypertension risk among middle-aged and elderly African ancestry men. Additional studies are needed to elucidate the mechanisms behind this association, and to confirm our findings in other populations.