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Objectives. To assess the effectiveness of a structured dynamic relaxation program for “Pain Management with Sophrology” in chronic pain patients. Methodology. A prospective, open-label, controlled, non-randomized pre-post-test study was conducted. A total of 91 patients started the study; sophrology group (N = 44), no-intervention control group (N = 47). Questionnaires used: Hospital Anxiety and Depression Scale (HADS), Visual Analogue Scale (VAS), and General Health Questionnaire-28 (GHQ-28). Results. In total, 88 patients finished the study; the dropout rate was 7% (N = 3) in the sophrology group (N = 41).Between-group analysis. Statistically significant differences were found across all HADS, VAS, and GHQ-28 subscales (<0.001) in favor of the sophrology group. Within-group analysis. Significant differences were observed across all HADS, VAS, and GHQ-28 subscales (p<0.001), regardless of gender and age. Large effect sizes (Cohen’s d) were observed: HADS (1.1–1.15), VAS (0.99), and GHQ-28 (0.95–2.16). In the control group, effect sizes were small or absent. Conclusion. In a prospective, controlled, non-randomized study, the “Pain Management with Sophrology” program (12 1-hour sessions over 6 weeks) reduced symptoms of pain, anxiety, depression, and somatization, improved social functioning, and enhanced daily activities in ambulatory patients with chronic pain, as measured by the applied questionnaires.