Background: Sternal wound infection is a catastrophic complication after open heart surgery, so many studies have evaluated the effect of negative pressure wound therapy (NPWT) to prevent it. Objective: This study aimed to evaluate the impact of incisional negative pressure wound therapy on the wound healing process after midline sternotomy in open heart surgery.  Patients and methods: 100 patients who underwent open heart surgery with midline sternotomy were included. They were divided equally into two groups: Group A included 50 patients who had negative pressure wound therapy and group B that contained 50 patients who had conventional wound dressing. Results: Patients who underwent negative pressure wound therapy had significantly lower incidences of TLC rising (P=0.043), and CRP rising (P=0.017), significantly lower incidences of overall post-operative wound infection (P=0.025), significantly lower post-operative progression to deep wound infection (P=0.024), significantly lower need for post-operative deep wound intervention (P=0.012), significantly shorter ICU stay (P=0.001), as well as shorter hospital stay (P=0.018) when compared to patients who had conventional wound dressing. Also, no mortality was detected among our studied patients. Conclusion: Negative pressure wound therapy was superior to conventional wound dressing as it was associated with significantly lower incidences of TLC and CRP rising, significantly lower incidences of overall post-operative wound infection and post-operative deep wound infection, significantly lower need for post-operative deep wound intervention, as well as significantly shorter ICU stay (due to readmission) and hospital stay, when compared to conventional wound dressing.