To quantify the risk of knee pain exacerbation associated with temperature, relative humidity, air pressure and precipitation in persons with knee osteoarthritis.a web-based case-crossover study was conducted. Participants with a diagnosis of symptomatic, radiographic knee osteoarthritis were measured at baseline and followed for 3 months. Participants were instructed to log on to the study website if they perceived experiencing knee pain exacerbation (hazard period). Pain exacerbation was defined as an increase of ≥ 2 on a 0-10 numeric rating scale from the participant's mildest pain reported at baseline. A time-stratified case-crossover study was conducted to anchor the corresponding hazard date to 4 control periods within a particular 35-day interval. Data on maximum and minimum temperature ((o)C), relative humidity (%), barometric pressure (hPa) and precipitation (mm) were obtained for the hazard and control periods from the publicly available meteorological database of the Australian Bureau of Meteorology. The associations were assessed using conditional logistic regression.Of the 345 participants recruited, 171 participants (women: 64%, mean age: 62 years, mean BMI: 30.2 kg/m2) experienced at least one episode of pain exacerbation, yielding 1,425 observations included in the analyses. There was no apparent association between temperature, relative humidity, air pressure or precipitation and risk of knee pain exacerbation.Despite anecdotal reports from patients, change in weather factors does not appear to influence the risk of pain exacerbation in persons with knee osteoarthritis. Additional studies should quantify the association of weather and risk of pain exacerbation in regions with more extreme weather conditions.