Background: The primary aim was to compare the outcomes of locked plating of closed distal femur periprosthetic and non-periprosthetic fractures by testing the hypothesis that outcomes would be worse in the periprosthetic group. The secondary aim of this study was to identify risk factors for non-union. Methods: A single-center study over an 8-year period utilizing a retrospective cohort design was performed. Sixty-eight patients with periprosthetic fractures and 57 patients with non-periprosthetic fractures met inclusion criteria for the study. There was a significant difference between groups in mean age (80.1 years periprosthetic vs. 70.9 years non-periprosthetic (p < 0.001)). Statistical analysis between groups was used to assess the outcomes of time to union, incidence of non-union, post-operative functionality, incidence of complications, progression to revision surgery, and mortality. A secondary multivariable analysis was used to assess risk factors for non-union and factors positively associated with union. Results: There were no significant differences in outcomes between groups. Union rates were 83.8% (57/68) in the periprosthetic group and 78.9% (45/57) in the non-periprosthetic group (p = 0.648). Comminution was identified as a significant risk factor for non-union (p = 0.005). Use of a submuscular technique had a significant positive association with union (p = 0.006). Conclusions: Outcomes of surgical treatment for periprosthetic and non-periprosthetic distal femur fractures are similar. There is a significant risk of non-union in locked plating of both groups.