The factors affecting the outcomes of segmental femoral shaft fractures are currently unknown. We evaluated the outcomes of intramedullary (IM) nail fixation and investigated factors affecting nonunion of femoral shaft segmental fractures. A total of 38 patients who underwent IM nail fixation for femoral shaft segmental fractures (AO/OTA 32C2) at three university hospitals with a minimum 1-year follow-up period were retrospectively reviewed. The patients were divided into union (n = 32) and nonunion (n = 6) groups. We analyzed smoking status, diabetes mellitus, location of the segmental fragment, segment comminution, filling of the IM nail in the medullary canal, residual gap at the fracture site, use of a cerclage wire or blocking screws as factors that may affect the surgical outcome. In the union group, the average union time was 5.4 months (4–9 months). In the nonunion group, five patients required additional surgery within an average of 7.2 months (5–10 months) postoperatively, whereas one patient remained asymptomatic and did not require further intervention. On comparing the two groups, insufficient canal filling of the IM nail (union, 25.0%; nonunion, 83.3%;p= 0.012) and the presence of a residual gap at the fracture site after reduction (union, 31.3%; nonunion, 83.3%;p= 0.027) were significantly different. In the multivariate analysis, only insufficient canal filling of the IM nail was found to be a factor affecting nonunion, with an odds ratio of 13.3 (p= 0.036). In this study, a relatively high nonunion rate (15.8%) was observed after IM nail fixation. Insufficient IM nail canal filling and a residual gap at the fracture site post reduction were factors affecting segmental femoral shaft fracture nonunion after IM nail fixation.