Abstract Objective The purpose of this study was to examine the effects of connective tissue manipulation (CTM) on the severity of constipation and health-related quality of life in individuals diagnosed with chronic constipation. Methods Fifty patients with a diagnosis of chronic constipation according to Rome III criteria were recruited and randomized to an intervention (n = 25) or control group (n = 25). The intervention group received CTM in addition to the lifestyle advice, whereas the control group was given only lifestyle advice for constipation. All assessments were performed at baseline and at the end of 4 weeks. The primary outcome measure was the Constipation Severity Instrument. Secondary outcomes included Patient Assessment of Constipation Quality of Life Questionnaire, Bristol Stool Scale, and 7-day bowel diary. Differences between groups were analyzed with t tests, Mann-Whitney U test and χ2 test. Results Compared with the control group, subjects in the intervention group reported significantly greater improvement in total and subscale scores of the Constipation Severity Instrument and Patient Assessment of Constipation Quality of Life Questionnaire ( P < .05). Based on the results from bowel diaries, the improvements in the number of bowel movements, duration of defecation, stool consistency, and the feeling of incomplete evacuation in the intervention group were also significantly more than the control group ( P < .05). Conclusion This study showed that CTM and lifestyle advice were superior to reducing symptoms of constipation and quality of life compared with lifestyle advice alone for patients with chronic constipation.