Introduction Fracture-related infection (FRI) is a severe post-traumatic complication which is occasionally accompanied by a deficient or even avital soft-tissue envelope. In these cases, a thoroughly planned orthoplastic approach is imperative as a vital and intact soft-tissue envelope is mandatory to achieve fracture union and infection eradication. The aim of this study was, to analyse if soft-tissue reconstruction (STR) without complications is associated with a better long-term outcome compared to FRI patients with STR complications. In particular, it was investigated if primary flap failure represented a risk factor for compromised fracture union and recurrence of infection. Patients and Methods Patients with a lower leg FRI requiring STR (local, pedicled and free flaps) who were treated from 2010-18 at the University Hospital Basel were included in this retrospective analysis. The main outcome measure was the success rate of STR, further outcome measures were fracture nonunion and recurrence of infection. Results Overall, 145 patients with lower leg FRI were identified, of whom 58 (40%) received STR (muscle flaps: n = 38, fascio-cutaneous flaps: n=19; composite osteo-cutaneous flap: n = 1). In total seven patients required secondary STR due to primary flap failure. All failures and flap-related complications occurred within the first three weeks after surgery. Secondary STR was successful in all cases. A high Charlson Comorbidity Index Score was a significant risk factor for flap failure (p = 0.011). Out of the 43 patients who completed the 9-month follow-up, 11 patients presented with fracture nonunion and 12 patients with a recurrent infection. Polymicrobial infection was a significant risk factor for fracture nonunion (p = 0.002). Primary flap failure was neither a risk factor for compromised fracture consolidation (p = 0.590) nor for recurrence of infection (p = 0.508). Conclusion: A considerable number of patients with lower-leg FRI required STR. This patient subgroup is complex and rich in complications and the long-term composite outcome demonstrated a high rate of compromised fracture consolidation and recurrent infections. It appears that secondary STR should be performed, as primary flap failure was neither a risk factor for compromised fracture consolidation nor for recurrence of infection. We propose to monitor these patients closely for three weeks after STR.