Risks of third-trimester amniocentesis are considered minimal; however, only case series have been reported. We performed a case-control study in which women undergoing third-trimester amniocentesis were matched with controls undergoing antenatal testing for similar indications to determine adverse outcomes associated with the procedure. Cases undergoing amniocentesis at > 32 weeks for fetal lung maturity assessment followed by antepartum testing with nonstress test and amniotic fluid index determination were matched with controls undergoing only antepartum testing based on gestational age at testing and maternal age. The main outcome variable was a composite occurrence of obstetric complications within 48 hours of testing, including urgent delivery, placental abruption, premature rupture of membranes (PROM), perinatal death, or Apgar score at 5 minutes < 7. Statistical analysis included Fisher's exact test and Student T-test, with P < 0.05 considered significant. A total of 167 matched pairs of patients fulfilled the study criteria. Indications for both amniocentesis and antepartum testing, which included diabetes, preterm labor, and cholestasis, were similar in the two groups. As expected, gestational age at sampling/testing (36.4 +/- 1.4 [mean +/- standard deviation] versus 36.6 +/- 1.7 weeks; P = 0.2) and maternal age (31.4 +/- 5.8 versus 31.5 +/- 6.3 years; P = 0.9) were not different between cases and controls. The rate of the main outcome variable within 48 hours of testing was 0 of 167 among cases and 1 of 167 among controls. Amniocentesis in the third trimester is not associated with increased risk of urgent delivery, placental abruption, PROM, Apgar score at 5 minutes < 7, or perinatal death within 48 hours of the procedure.