Hydrogen isotope ratios of long-chain alkenones (δ2HC37 ratios) have been shown to correlate with salinity in several culture studies. However, it is uncertain how applicable the δ2HC37-salinity relationship is to reconstruct past salinity. δ2HC37 ratios were measured on sediments from a drill core (ODP site 1234) at the Chilean Margin covering the last ~150 kyr. High δ2HC37 values correspond to glacial time periods and interglacial periods are characterized by lower δ2HC37 values, aligning with δ18O ratios measured on planktonic foraminifera from the same core. Effects of parameters such as species composition, the δ2H-δ18O relationship used for ice volume corrections, and nutrient or light controlled growth rate, do not appear to significantly alter δ2HC37 ratios at ODP 1234. We use linear regression equations from batch culture experiments, marine surface sediments, and suspended particulate organic matter to quantitatively characterize salinity changes over the last ~150 kyr at ODP 1234. However, most of these equations yield larger salinity shifts than previously suggested, a phenomenon also observed for other δ2HC37 records. This suggests that the paleosensitivity of δ2HC37 ratios to salinity is larger in the geologic record than has been observed in any modern environment or laboratory settings, or that glacial to interglacial salinity shifts might be larger than currently believed.