New commercial liquid light guides have an advantage over fiberoptic bundles regarding breakage during clinical handling. We investigate the quality of clinical data collection using liquid versus fiber bundles as receivers. A four-wavelength NIRO-500 near-IR spectrophotometer is used with single-terminal fiber bundles, multiterminal fiber bundles, or a single-terminal liquid light guide as receivers. Repeated 3-min trials are done using a stable phantom, an unstable phantom, and the human forearm. A least-squares linear best-fit line and its root mean square error (RMSE), a measure of signal noise, are derived for each wavelength of each trial. The mean and standard deviations for the RMSEs of the single-terminal fiber optic receiving cable are derived for comparison standards. The liquid light guides have 51 to 174% greater signal noise with RMSEs 2 to 12 standard deviations above the mean of the single-terminal fiber bundle. The multiterminal fiber bundles have 49% less to 32% greater signal noise and had RMSEs within 1 to 4 standard deviations above the mean of the single-terminal fiber bundle. These comparisons suggest fiber optic bundles are preferable for clinical near-IR spectroscopy (NIRS) applications requiring low signal noise.