The aim of this study was to identify the effects of connective tissue manipulation (CTM) in primary dysmenorrhea (PD) in a randomized, placebo-controlled design. Thirty-eight nulliparous women with PD were randomly allocated into 3 groups: CTM (n = 13), placebo therapeutic ultrasound (US) (n = 13), and control (n = 12). The primary outcome measure was the maximum and mean menstrual pain intensity at the last menstrual period on the visual analogue scale (VAS). Secondary outcome measures were menstrual symptom frequency and distress score, the number of analgesic/anti-inflammatory drugs used during the last menstrual period, and perception of improvement in dysmenorrhea severity via interventions. The chi-square test and analysis of variance were used to determine within-group and between-group differences. Statistical significance level was determined as p < 0.05. Compared with the placebo US and control groups, it was observed that menstrual pain (VAS mean and VAS maximum), menstrual symptom frequency, and distress level decreased more after treatment (T2) and the 3-month follow-up (T3) in de CTM group (p < 0.001, p = 0.001, p = 0.014, p = 0.015, respectively). There was no difference between the groups in terms of analgesic/anti-inflammatory drugs use (p > 0.05). The rate of individuals reporting perceived improvement at the end of intervention period was higher in the CTM group than in the placebo-US and control groups (p < 0.001). In the 3rd month follow-up, there was no difference between groups in the perception of improvement (p > 0.05). CTM is superior to placebo intervention and control in improving menstrual pain and other menstrual symptoms in PD in the short-term. On the other hand, when the application is terminated, this superiority seems to disappear during the follow-up period.