Background: Gustilo-Anderson grade IIIb open fractures of the lower limb present significant management challenges. This study evaluated the outcomes of negative pressure wound therapy (NPWT) for these complex injuries at a tertiary care center in Tripura, India. Methods: This prospective observational study included 20 adult patients with Gustilo-Anderson grade IIIb open lower limb fractures treated between May 2020-April 2021. All patients received initial trauma management, wound debridement, and external fixation followed by NPWT. Outcomes assessed included time to granulation tissue formation, infection rates, and time to definitive surgery. Results: The mean age was 31.6 ± 9.4 years, with a male predominance. Road traffic accidents caused 90% of injuries. Healthy granulation tissue developed in 90% of patients within 72 hours of NPWT initiation. The mean time to complete granulation coverage was 14.4 ± 4.7 days. Superficial infection rates decreased from 7 pre-NPWT to 3 post-NPWT. Most patients (84.2%) were ready for definitive surgery by 5 weeks post-external fixation. Conclusion: NPWT appears effective in promoting wound healing, controlling infections, and optimizing the wound bed for definitive surgery in Gustilo-Anderson grade IIIb open lower limb fractures. However, larger trials are needed to establish standardized protocols and long-term outcomes.