STUDY DESIGN: Randomized clinical trial. Objectives To compare the blood pressure (BP) and heart rate (HR) response of healthy volunteers to posteriorly directed (anterior-to-posterior [AP]) pressure applied to the cervical spine versus placebo. BACKGROUND: Manual therapists employ cervical spine AP mobilizations for various cervical-shoulder pain conditions. However, there is a paucity of literature describing the procedure, cardiovascular response, and safety profile. METHODS: Thirty-nine (25 female) healthy participants (mean ± SD age, 24.7 ± 1.9 years) were randomly assigned to 1 of 2 groups. Group 1 received a placebo, consisting of light touch applied to the right C6 costal process. Group 2 received AP pressure at the same location. Blood pressure and HR were measured prior to, during, and after the application of AP pressure. One-way analysis of variance and paired-difference statistics were used for data analysis. RESULTS: There was no statistically significant difference between groups for mean systolic BP, mean diastolic BP, and mean HR (P >.05) for all time points. Within-group comparisons indicated statistically significant differences between baseline and post-AP pressure HR (-2.8 bpm; 95% confidence interval: -4.6, -1.1) and between baseline and post-AP pressure systolic BP (-2.4 mmHg; 95% confidence interval: -3.7, -1.0) in the AP group, and between baseline and postplacebo systolic BP (-2.6 mmHg; 95% confidence interval: -4.2, -1.0) in the placebo group. No participants reported any adverse reactions or side effects within 24 hours of testing. CONCLUSION: AP pressure caused a statistically significant physiologic response that resulted in a minor drop in HR (without causing asystole or vasodepression) after the procedure, whereas this cardiovascular change did not occur for those in the placebo group. Within both groups, there was a small but statistically significant reduction in systolic BP following the procedure.