The Martin (or iron) hypothesis suggests that ocean iron fertilization (OIF) could be an effective method for stimulating oceanic carbon sequestration through the biological pump in iron-limited, high-nutrient, low-chlorophyll (HNLC) regions. To test the Martin hypothesis, 13 artificial OIF (aOIF) experiments have been performed since 1990 in HNLC regions. These aOIF field experiments have demonstrated that primary production (PP) can be significantly enhanced by the artificial addition of iron. However, except in the Southern Ocean (SO) European Iron Fertilization Experiment (EIFEX), no significant change in the effectiveness of aOIF (i.e., the amount of iron-induced carbon export flux below the winter mixed layer depth, MLD) has been detected. These results, including possible side effects, have been debated amongst those who support and oppose aOIF experimentation, and many questions concerning the effectiveness of scientific aOIF, environmental side effects, and international aOIF law frameworks remain. In the context of increasing global and political concerns associated with climate change, it is valuable to examine the validity and usefulness of the aOIF experiments. Furthermore, it is logical to carry out such experiments because they allow one to study how plankton-based ecosystems work by providing insight into mechanisms operating in real time and under in situ conditions. To maximize the effectiveness of aOIF experiments under international aOIF regulations in the future, the authors therefore suggest a design that incorporates several components. (1) Experiments conducted in the center of an eddy structure when grazing pressure is low and silicate levels are high (e.g., in the SO south of the polar front during early summer). (2) Shipboard observations extending over a minimum of ∼ 40 days, with multiple iron injections (at least two or three iron infusions of ∼ 2000 kg with an interval of ∼ 10–15 days to fertilize a patch of 300 km2 and obtain a ∼ 2 nM concentration). (3) Tracing of the iron-fertilized patch using both physical (e.g., a drifting buoy) and biogeochemical (e.g., sulfur hexafluoride, photosynthetic quantum efficiency, and partial pressure of CO2) tracers. (4) Employment of neutrally buoyant sediment traps (NBST) and application of the water-column-derived thorium-234 (234 Th) method at two depths (i.e., just below the in situ MLD and at the winter MLD), with autonomous profilers equipped with an underwater video profiler (UVP) and a transmissometer. (5) Monitoring of side effects on marine/ocean ecosystems, including production of climate-relevant gases (e.g., nitrous oxide, N2O; dimethyl sulfide, DMS; and halogenated volatile organic compounds, HVOCs), decline in oxygen inventory, and development of toxic algae blooms, with optical-sensor- equipped autonomous moored profilers and/or autonomous benthic vehicles. Lastly, we introduce the scientific aOIF experimental design guidelines for a future Korean Iron Fertilization Experiment in the Southern Ocean (KIFES).