The extraction of pyrethrins from chrysanthemum flowers has been performed using supercritical CO2 (SC-CO2) extraction coupled to fractional separation, with the aim of producing complete and selective extraction of these insecticidal principles. 90bar, 40°C were selected as the operative conditions for a first step of extraction, to work at moderate SC-CO2 density; two separators in series operating at −10°C and at a pressure equal to that of extraction, and 25°C, 15bar, were used for fractional separation, respectively. A second SC-extraction step, performed at 200bar 40°C, demonstrated that many undesired compounds were co-extracted at these process conditions. The comparison with liquid extraction, using petroleum ether, showed that using SC-CO2 and an exhaustive processing, 30% more pyrethrins were extracted. Using the fractional separation, the produced extracts contained about 99% w/w pyrethrins if the process was stopped after about 80min. Another suggested duration of the extraction process can be set at about 250min, at which about 63% w/w pyrethrins were contained in the extracted material. The adopted process strategy could be readily extended to the supercritical processing of several other materials and to the industrial scale.