Objective Lateral wedge insoles are intended to reduce biomechanical risk factors of medial knee osteoarthritis (OA) progression, such as increased knee joint load; however, there has been no definitive consensus on this topic. The aim of this systematic review and meta-analysis was to establish the within-subject effects of lateral wedge insoles on knee joint load in people with medial knee OA during walking. Methods Six databases were searched from inception until February 13(th) 2015. Included studies reported on the immediate biomechanical effects of lateral wedge insoles in people with medial knee osteoarthritis during walking. Primary outcomes of interest relating to the biomechanical risk of disease progression were the 1(st) and 2(nd) peak external knee adduction moment (EKAM) and knee adduction angular impulse (KAAI). Eligible studies were pooled using random-effects meta-analysis. Results Eighteen studies were included with a total of 534 participants. Lateral wedge insoles resulted in a small but statistically significant reduction in the 1(st) peak EKAM (SMD: -0.19; 95% CI -0.23 - -0.15) and 2(nd) peak EKAM (SMD: -0.25; 95% CI -0.32 - -0.19) with a low level of heterogeneity (I(2) = 5% and 30%, respectively). There was a favourable but small reduction in the KAAI with lateral wedge insoles (SMD: -0.14; 95% CI -0.21 - -0.07, I(2 =) 31%). Risk of methodological bias scores (Quality Index) ranged from 8 to 13 out of 16. Conclusions Lateral wedge insoles cause small reductions in the EKAM and KAAI in people with medial knee OA during walking. Current evidence demonstrates that lateral wedge insoles appear ineffective at attenuating structural changes in people with medial knee OA as a whole and may be better suited to targeted use in biomechanical phenotypes associated with larger reductions in knee load. This article is protected by copyright. All rights reserved.