ABSTRACT: OBJECTIVE:To determine if varus thrust, a bowing out of the knee during gait (i.e., the first appearance or worsening of varus alignment during stance), is associated with incident and progressive knee osteoarthritis (OA), we undertook an Osteoarthritis Initiative ancillary study. We further considered hypothesized associations adjusted for static alignment, anticipating some attenuation. METHODS:Gait was observed for the presence of thrust by 1 of 2-3 examiners per study site at 4 sites. In eligible knees, incident OA was defined as subsequent incident Kellgren/Lawrence grade ?2, whole- and partial-grade medial joint space narrowing (JSN), and annualized loss of joint space width (JSW); progression was defined as medial JSN and JSW loss. Outcome measures were assessed for up to 7 years of follow-up. Analyses were knee-level, using multivariable logistic and linear regression with generalized estimating equations to account for between-limb correlation. RESULTS:The incident OA sample included 4,187 knees (2,610 persons); the progression sample included 3,421 knees (2,284 persons). In knees with OA, thrust was associated with progression as assessed by each outcome measure, with adjustment for age, sex, body mass index, and pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. In knees without OA, varus thrust was not associated with incident OA or other outcomes. After adjustment for alignment, the thrust-progression association was attenuated, but an independent association persisted for partial-grade JSN and JSW loss outcome models. WOMAC pain and alignment were consistently associated with all outcome measures. Within the stratum of varus knees, thrust was associated with an increased risk of progression. CONCLUSION:Varus thrust visualized during gait is associated with knee OA progression and should be a target of intervention development.