Surgical resection remains the most effective treatment option for patients with early stage non-small cell lung cancer; however, comorbidities and poor pulmonary reserve often limit the extent of resection. Limited resections are associated with a twofold to threefold increase in locoregional recurrence, suggesting that microscopic disease remains near the resection margin. We hypothesized that local delivery of paclitaxel through 100-nm expansile polymer nanoparticles (pax-eNP) immediately after tumor resection could prevent local recurrence.Primary tumors, initiated on the dorsum of C57BL/6J mice through subcutaneous injection of 750,000 Lewis lung carcinoma cells, were excised when tumor volume reached 300 mm 3 . After resection, animals were randomized to receive 300 μg paclitaxel intravenously or as pax-eNP locally at the tumor resection site versus unloaded eNP or saline controls.In all mice receiving saline, unloaded eNP, or paclitaxel intravenously, visible local tumor recurrence developed at a median of 6 days. In contrast, tumor recurrence after pax-eNP was delayed to 10 days (pax-eNP versus all other groups, Kaplan-Meier, p < 0.05). Delay in local recurrence was associated with increased survival in the pax-eNP group (16 days) versus all other groups (11 and 12 days, p < 0.05).The pax-eNP placed at the time of surgical resection delayed local tumor recurrence and modestly prolonged survival in a murine Lewis lung carcinoma recurrence model.