A comparatively simple, rapid, low-blank, high-precision and reproducible technique for Nd isotope analysis (143Nd/144Nd) of trace amounts (1–5 ng) of Nd by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) was developed and is reported here. The technique utilizes a combination of a high-sensitivity desolvator (Aridus II or APEX-IR) and high-efficiency Jet-sample/X-skimmer cones, together with high-yield pre-concentration and column chemistry, to achieve optimal conditions for Nd isotope determination in natural materials with a variety of Nd-depleted matrices. This new method was validated by analyzing a series of international reference materials (RMs), which span a wide range of the Nd isotopic composition and cover different sample matrices in order to provide a useful benchmark for future studies. The long-term precision of 143Nd/144Nd (±0.000016, 2SD) for a sample size of ca. 1.25 ng Nd is a factor of 5 better than the existing high-sensitivity MC-ICP-MS methods using <2 ng of Nd and is comparable to the best TIMS methods. Replicate analyses of the RMs, including JNdi-1 (0.512116 ± 0.000016, 2SD), AGV-1 (0.512794 ± 0.000013, 2SD), BHVO-1 (0.512992 ± 0.000015, 2SD), Nod-P-1 (0.512430 ± 0.000015, 2SD) and two sets of synthetic solutions for seawater and calcium carbonate matrices, are in excellent agreement with the published values, demonstrating the robustness of the present protocol for natural samples with different matrices. A depth profile of the seawater Nd isotopes near the Bermuda Atlantic Time-series Study station was also analyzed for comparison, and is identical to the reported seawater profile in this region. Applying this improved technique, we are able to generate high-precision and reproducible Nd isotope data for Nd-depleted natural materials, such as seawater, continental runoff, benthic fluxes at continental margins, and marine biogenic carbonate, which can provide pertinent and complementary information about the marine Nd cycle and past ocean circulation.