Background Mounting evidence has demonstrated a role of psychosocial stressors such as discrimination in hypertension and cardiovascular diseases. The objective of this study was to provide the first instance of research evidence examining prospective associations of workplace discrimination with onset of hypertension. Methods and Results Data were from MIDUS (Midlife in the United States), a prospective cohort study of adults in the United States. Baseline data were collected in 2004 to 2006, with an average 8-year follow-up period. Workers with self-reported hypertension at baseline were excluded, yielding a sample size of 1246 participants for the main analysis. Workplace discrimination was assessed using a validated 6-item instrument. During follow-up with 9923.17 person-years, 319 workers reported onset of hypertension, and incidence rates of hypertension were 25.90, 30.84, and 39.33 per 1000 person-years among participants with low, intermediate, and high levels of workplace discrimination, respectively. Cox proportional hazards regression analyses demonstrated that workers who experienced high exposure to workplace discrimination, compared with workers with low exposure, had a higher hazard of hypertension (adjusted hazard ratio, 1.54 [95% CI, 1.11-2.13]). Sensitivity analysis excluding more baseline hypertension cases based on additional information on blood pressure plus antihypertensive medication use (N=975) showed slightly stronger associations. A trend analysis showed an exposure-response association. Conclusions Workplace discrimination was prospectively associated with elevated risk of hypertension among US workers. The adverse impacts of discrimination on cardiovascular disease have major implications for workers' health and indicate a need for government and employer policy interventions addressing discrimination.