The objectives of this study were to evaluate the performance of the NucliSens easyMAG platform for nucleic acid extraction from different clinical specimens compared to NucliSens miniMAG platform and manual QIAGEN extraction. The NucliSens easyMAG and the NucliSens miniMAG showed equal performance on 215 throat swabs since real-time nucleic acid sequence-based amplification scored the same samples positive for Mycoplasma pneumoniae (n ؍ 9) and Chlamydia pneumoniae (n ؍ 5) RNAs, although internal control RNA was slightly better detected with the NucliSens easyMAG (99.3% versus 96.8%). NucliSens easyMAG extracted nucleic acids more efficiently (higher recovery and/or fewer inhibitors) compared to QIAGEN extraction by showing, on average, lower Ct values in real-time LightCycler PCR, although 4 individual specimen out of 45 were found positive only with QIAGEN. For nine M. pneumoniae-positive throat swabs, the mean difference in Ct values between NucliSens easyMAG extraction and QIAGEN extraction was ؊2.26 (range, ؊5.77 to ؉0.60); for the detection of five C. pneumoniae-positive throat swabs, the average difference in Ct values between the two methods was ؊3.38 (range, ؊6.62 to ؊2.02); and for the detection of cytomegalovirus in 24 blood samples, the mean difference in Ct values between the two methods was ؊0.95 (range, ؊5.51 to ؉1.68). The NucliSens easyMAG is considerably easier to perform, efficiently extracts nucleic acids from throat swabs and whole blood, is automated, and has high throughput.Numerous nucleic acid amplification tests are performed daily in an increasing number of clinical laboratories because of their high sensitivities and specificities. Further developments in the field have decreased the turnaround time and hands-on time. Nucleic acid extraction systems with high flexibilities in the type and number of samples to be handled and with a wide range of sample and elution volumes and short turnaround times provide a further advantage to adapt amplification techniques to clinical diagnostic requirements.A high-quality nucleic acid extract is expected to be free of amplification inhibitors and other substances that might affect enzyme substrates, and the target should be optimally recovered.The NucliSens easyMAG platform (bioMérieux, Boxtel, The Netherlands) is a second-generation system for automated isolation of nucleic acids from clinical samples based upon silica extraction technology (3). It is a benchtop instrument with the same reagents as the manual version, i.e., NucliSens miniMAG platform (bioMérieux) (4,14,17,19). Manual steps are limited to the loading of samples, reagents, and disposables. One to 24 samples can be analyzed in one run. The extraction method is universal and can be applied to a broad range of different specimens such as blood, sputum, serum, and throat swabs. The instrument can be used in combination with different amplification methods such as nucleic acid sequence-based amplification (NASBA) or PCR. Limited data are available on the NucliSens easyMAG extraction ...