Removal of carotid body (CB) improves animal models of hypertension (HTN) and heart failure, via withdrawal of chemoreflex-induced sympathetic activation. Effect of CB tumor (CBT) resection on blood pressure (BP) in subjects with HTN is unknown. A retrospective analysis of 20 subjects with HTN (BP≥140/90 mmHg or anti-hypertensives use) out of 134 with CBT resection. Short-term (30 days from surgery) and long-term (slope of regressions on time over the entire follow-up) changes in BP and heart rate were adjusted for covariates (interval between readings, total follow-up, number of readings and changes in therapy). Age and duration of HTN were 56±4 and 9±5 years. Adjusted short-term decreases in systolic (SBP: -9.9±3.1, p<0.001) and pulse pressures (PP: -7.9±2.7, p<0.002) were significant and correlated with their respective long-term changes (SBP: r=0.47, p=0.047; PP: r=0.54, p=0.019). There was a strong relationship between adjusted short-term changes in SBP and PP (r=0.64, p<0.004). Six (50% of responders or 33% of the total) had short-term falls of SBP ≥10 mmHg and of PP ≥ 5 mmHg. First study to show that unilateral CBT resection is associated with sustained reduction of BP in hypertensive patients. Targeted CB chemoreflex removal could play a role in the therapy of human HTN.