Myofascial pain syndrome, thought to be the main cause of neck pain and shoulder muscle tenderness in the working population, is characterized by myofascial trigger points (MTrPs). This study aimed to examine the immediate and short-term effect of the combination of two therapeutic techniques for improving neck pain and muscle tenderness in male patients with upper trapezius active MTrPs. This study was a pretest-posttest single-blinded randomized controlled trial. Sixty male subjects with mechanical neck pain due to upper trapezius active MTrPs were recruited and randomly allocated into group A, which received muscle energy technique (MET) and ischemic compression technique (ICT) along with conventional intervention; group B, which received all the interventions of group A except ICT; and group C, which received conventional treatment only. Baseline (Pr), immediate postintervention (Po), and 2-week follow-up (Fo) measurements were made for all variables. Pain intensity and pressure pain threshold (PPT) were assessed by a visual analog scale (VAS) and pressure threshold meter, respectively. All the three groups received their defined intervention plans only. Repeated-measures analysis of variance was used to perform intra- and intergroup analyses. Cohen’s d test was used to assess the effect size of the applied interventions within the groups. The intergroup analysis revealed significant differences among groups A, B, and C in VAS and PPT at Po (VAS-Po: F = 13.88, ; PPT-Po: F = 17.17, ) and even after 2 weeks of follow-up (VAS-Fo: F = 222.35, ; PPT-Fo: F = 147.70, ). Cohen’s d revealed a significant treatment effect size within all groups except group C (only significant for VAS-Po–VAS-Pr: mean difference = 1.33, , d = 1.09); however, it showed a maximum effect size in group A for its variables (VAS-Fo–VAS-Pr: mean difference = 5.27, , d = 4.04; PPT-Fo–PPT-Pr: mean difference = 2.14, , d = 3.89). Combination therapies (MET plus ICT) showed immediate and short-term (2-week follow-up) improvements in neck pain and muscle tenderness in male patients with upper trapezius active MTrPs.