African Americans have a greater prevalence of hypertension and diabetes compared with white Americans, and both autonomic dysregulation and inflammation have been implicated in the etiology of these disease states. The purpose of this study was to examine the cardiac autonomic and systemic inflammatory response to resistance training in young African-American and white men. Linear (time and frequency domain) and nonlinear (sample entropy) heart rate variability, baroreflex sensitivity, tonic and reflex vagal activity, and postexercise heart rate recovery were used to assess cardiac vagal modulation. C-reactive protein (CRP) and white blood cell count were used as inflammatory markers. Twenty two white and 19 African-American men completed 6 wk of resistance training followed by 4 wk of exercise detraining (Post 2). Sample entropy, tonic and reflex vagal activity, and heart rate recovery were increased in white and African-American men following resistance training (P < 0.05). Following detraining (Post 2), sample entropy, tonic and reflex vagal activity, and heart rate recovery returned to baseline values in white men but remained above baseline in African-American men. While there were no changes in white blood cell count or CRP in white men, these inflammatory markers decreased in African-American men following resistance training, with reductions being maintained following detraining (P < 0.05). In conclusion, resistance training improves cardiac autonomic function and reduces inflammation in African-American men, and these adaptations remained after the cessation of training. Resistance training may be an important lifestyle modification for improving cardiac autonomic health and reducing inflammation in young African-American men.