Introduction. Advanced wound management of complex surgical wounds remains a significant challenge as more patients are being admitted to the hospital with infected wounds. Reducing recurrent infections and promoting granulation tissue formation are essential to overall wound healing. Negative pressure wound therapy (NPWT) has been widely practiced for 2 decades for the management of such wounds, but NPWT with instillation and dwell time (NPWTi-d) is a relatively recent adjunctive treatment of wounds that require serial debridements. Objective. This study evaluates the advantages and disadvantages of NPWTi-d alone as well as NPWTi-d as an adjunct to standard NPWT in the treatment of complex wounds in patients with serious comorbidities. Materials and Methods. In this case series, the NPWTi-d group was given instillation therapy only. In the combined group, instillation therapy was applied and then, as the bioburden in the wound decreased, NPWT therapy was substituted. Repeated volumetric measurements and photographs of the wounds were taken. An approximate 50% decrease in wound dimensions, clearance of slough and necrotic tissue, and the appearance of healthy granulation tissue in the wound bed were considered as the endpoint of therapy. Results. Four cases in which only NPWTi-d was applied reached the endpoint with 1 to 3 dressings. In the other 4 cases, after NPWTi-d was applied, the bioburden was reduced to a great extent but the wound did not reach the end point. There were a few episodes of troubleshooting (eg, leakage alarm and blocking of the drainage tubes) in the system, and surrounding skin showed maceration. Hence, 2 to 4 courses of NPWT were substituted for the wound to reach the endpoint. Conclusions. In this study, NPWTi-d proved to be more effective in clearing the bioburden and reducing the number of surgeries for debridement. Complementing it with NPWT led to reduced episodes of troubleshooting and proved to be more cost-effective. Thus, NPWT may be considered as an adjunct therapy in select cases of complex wounds. However, more evidence is required.