Epidemiological studies may require noninvasive methods for off-site DNA collection. We compared the DNA yield and quality obtained using a whole-saliva collection device (Oragene™ DNA collection kit) to those from three established noninvasive methods (cytobrush, foam swab, and oral rinse). Each method was tested on 17 adult volunteers from our center, using a random crossover collection design and analyzed using repeated-measures statistics. DNA yield and quality were assessed via gel electrophoresis, spectophotometry, and polymerase chain reaction (PCR) amplification rate. The whole-saliva method provided a significantly greater DNA yield (mean ± SD = 154.9 ± 103.05 μg, median = 181.88) than the other methods (oral rinse = 54.74 ± 41.72 μg, 36.56; swab = 11.44 ± 7.39 μg, 10.72; cytobrush = 12.66 ± 6.19, 13.22 μg) (all pairwise P < 0.05). Oral-rinse and whole-saliva samples provided the best DNA quality, whereas cytobrush and swab samples provided poorer quality DNA, as shown by lower OD260/OD280 and OD260/OD230 ratios. We conclude that both a 10-ml oral-rinse sample and 2-ml whole-saliva sample provide sufficient DNA quantity and better quality DNA for genetic epidemiological studies than do the commonly used buccal swab and brush techniques.