Background: Cases of staphylococcal toxic shock syndrome (STSS) linked to the use of tampons have been reported on two separate occasions in the Pays de la Loire region, due to their close temporal proximity: two cases in 2013 and three cases in 2016, including a pair of twin sisters. This is a rare condition (approximately 20 cases reported annually in France by the National Reference Center (CNR) for Staphylococci), caused by a strain of Staphylococcus aureus that produces the TSST-1 toxin. Epidemiological and microbiological investigations were conducted to characterize these two clusters of cases. Methods: Cases were defined according to the clinical and laboratory criteria of the Centers for Disease Control and Prevention (United States). A questionnaire was completed for each case to describe the clinical and biological characteristics and tampon use among the young women. An individual risk of recurrence, characterized by the absence of serum antibodies against the TSST-1 toxin, was assessed by the National Reference Center for Staphylococci. Results: Among the 5 cases of CTS, 3 were definite and 2 others were probable but confirmed by bacteriology. Improper tampon use was described: the tampon was worn overnight (i.e., for more than eight hours) in 4 cases and used before the expected menstrual period in one case. All cases presented an increased risk of recurrence, necessitating the avoidance of vaginal tampon use. Discussion: The risk of developing menstrual-related CTS is most often associated with the misuse of tampons. It is important to assess the risk of recurrence in these young women by testing for protective antibodies against the toxin.