Purpose. Traditional knee osteoarthritis (OA) braces are usually indicated for a minority of patients with knee OA, as they are only suitable for those with unicompartmental disease affecting the tibiofemoral joint. A new assistive brace design is intended for use in a wider range of knee OA patients with heterogeneous symptoms characteristic of patellofemoral, tibiofemoral, or multicompartmental knee OA. The purpose of this case series was to explore whether the use of this novel “tricompartment offloader” (TCO) brace was associated with clinically relevant improvements in pain and function. Materials and Methods. A retrospective analysis of individuals with knee OA (
n
=
40
) was conducted to assess pain, function, physical activity, and use of medication and other treatments before and after brace use. Validated outcome measures including the Visual Analog Scale (VAS) and Lower Extremity Functional Scale (LEFS) were used to assess pain and physical function (primary outcome measures). Exploratory measures were used to quantify physical activity levels and use of medication and other treatments (secondary outcome measures). Results. Average total pain (VAS) scores decreased by 36.6 mm and physical function (LEFS) scores increased by 16.0 points following the use of the TCO brace. Overall, 70% of the participants indicated increased weekly physical activity and 60% reported a decrease in their use of at least one other treatment. Conclusions. Results from this case series suggest that the TCO brace shows strong potential to fill a conservative treatment gap for patients with heterogeneous symptoms of knee OA that are characteristic of patellofemoral or multicompartment disease. Further investigation is warranted.