Background. Failure to achieve delayed primary fascial closure (DPFC) is one of the main complications of open abdomen (OA), certainly when abdominal sepsis is present. This retrospective cohort study aims to evaluate the effect of combined therapy of vacuum-assisted mesh-mediated fascial traction and topical instillation (VAWCM-instillation) on DPFC in the open septic abdomen. Methods. The patients with abdominal sepsis who underwent OA using VAWCM were included and divided into the instillation and noninstillation (control) groups. The DPFC rate and other outcomes were compared between the two groups. Results. Between 2007 and 2013, 73 patients with open septic abdomen were treated with VAWCM-instillation and 61 cases with VAWCM-only. The DPFC rate in the instillation group was significantly increased (63% versus 41%, P = 0.011). The mortality with OA was similar (24.6% versus 23%, P = 0.817) between the two groups. However, time to DPFC (P = 0.003) and length of stay in hospital (P = 0.022) of the survivals were significantly decreased in the instillation group. In addition, VAWCM-instillation (OR 1.453, 95% CI 1.222-4.927, P = 0.011) was an independent influencing factor related to successful DPFC. Conclusions. VAWCM-instillation could improve the DPFC rate but could not decrease the mortality in the patients with open septic abdomen.