BACKGROUND: Amniocentesis is commonly performed to obtain a prenatal diagnosis. The most common indications for amniocentesis are abnormal foetal ultrasonography findings, followed by an increased risk of Down syndrome and advanced maternal age. The incidence of intra-amniotic infection is approximately 0.1%, and the risk of subclinical infection development after serial amniocentesis is no more than 0.5%. Septic shock is an unusual complication among cases of foetal loss associated with amniocentesis. Here, we report two cases of septic shock and multiple organ failure (MOF) after amniocentesis at mid-gestation. PRESENTATION OF CASES: Two women underwent genetic amniocentesis due to chromosomal aneuploidy. Prior to amniocentesis, the temperature, routine blood count, CRP and ultrasound findings were all normal. Genetic amniocentesis was performed under sterile conditions and without difficulty at 3P.M. A 22-gauge needle was passed into the right lower quadrant of the uterus, and 30 mL of clear fluid was extracted during the first attempt. They all complained of fever and chills and presented to the hospital within 48 hours after the amniocentesis. Foetal demise was found, and the patients rapidly developed septic shock. Despite vaginal delivery, curettage and antibiotic therapy, the patients deteriorated with the onset of MOF (myocardial damage, hypotension, renal insufficiency, low platelets). Blood cultures, discharge cultures and some tissue from the foetus all revealed Escherichia coli. The foul-smelling placenta was evacuated. There was gradual improvement with intensive monitoring. CONCLUSION: Uterine infection after amniocentesis leading to maternal sepsis is associated with a high morbidity and mortality rate. Our patients were able to survive without a hysterectomy due to the rapid administration of antibiotics and surgical intervention while being evaluated. Genetic counsellors and obstetric care providers should be aware of potential serious maternal morbidity and mortality that may occur subsequent to uncomplicated amniocentesis.