Infrared (IR) therapy is used for pain relief in patients with knee osteoarthritis (OA). However, IR’s effects on the cardiovascular system remain uncertain. Therefore, we investigated the local and systemic cardiovascular effects of monochromatic IR therapy on patients with knee OA in a double-blind, randomized, placebo-controlled study. Seventy-one subjects with knee OA received one session of 40 min of active or placebo monochromatic IR treatment (with power output of 6.24 W, wavelength of 890 nm, power density of 34.7 mW/cm2for 40 min, total energy of 41.6 J/cm2per knee per session) over the knee joints. Heart rate, blood pressure, and knee arterial blood flow velocity were periodically assessed at the baseline, during, and after treatment. Data were analyzed by repeated-measure analysis of covariance. Compared to baseline, there were no statistically significant group x time interaction effects between the 2 groups for heart rate (P=0.160), blood pressure (systolic blood pressure:P=0.861; diastolic blood pressure:P=0.757), or mean arterial blood flow velocity (P=0.769) in follow-up assessments. The present study revealed that although there was no increase of knee arterial blood flow velocity, monochromatic IR therapy produced no detrimental systemic cardiovascular effects.