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• A comprehensive assessment of the effectiveness of nitrification inhibitor DMPP under varying N rates and application timings on potato yield and NUE under tropical conditions was performed. • Compared to the conventional practice, split applied ammonium sulfate nitrate with DMPP (ASN + DMPP), at either 75% or 100% of recommended N rate (RNR), reduced N surplus in site-years with greater rainfall events and consistently increased potato tuber yield. • At reduced N rate (75% of RNR), single ASN + DMPP application at planting decreased potato yield, but at 100% of RNR potato production was not different from that receiving conventional N fertilization. • The mutual agronomic, economic, and environmental benefits of split-applied ASN + DMPP at 75% of RNR can contribute to the increased sustainability of tropical potato cropping systems. However, further studies are needed to confirm these benefits in other agro-ecosystems. Urea is the dominant nitrogen (N) fertilizer used for potato (Solanum tuberosum L.) cultivation in most parts of the world. Fertilizers containing a nitrification inhibitor (NI) claim to improve performance of crops including potato. No studies to date have conducted comprehensive assessment of N sources and the effectiveness of NI under varying N rates or application timings to enhance potato yield, tuber quality or N-use efficiency (NUE) in tropical regions. Three field experiments were conducted on irrigated sandy soils in southeastern Brazil to determine whether single or split application of ammonium sulfate nitrate (ASN) with the NI 3,4-dimethylpyrazole phosphate (DMPP) at reduced (75%) or recommended N rates (RNR, 100% = 160 kg ha-1) could improve yield, quality and/or NUE of 'Agata' potato over conventional split-applied urea at 100% of RNR. Compared to the conventional practice, split-applied ASN + DMPP, at either 75% or 100% of RNR, increased fresh tuber yield by an average of 15% across all site-years (SYs) and reduced N surplus in SYs with greater rainfall events suggesting that reactive N losses to the environment were also reduced. With split-applied ASN + DMPP at 75% of RNR, fresh tuber yield per unit of applied N increased by 34% compared to split-applied ASN + DMPP at 100% of RNR, and by 50–75% compared to a single application of ASN + DMPP at planting. These results demonstrate a mutually beneficial opportunity, where the rate of split-applied ASN + DMPP can be reduced by 25% while at the same time increasing yields, thus resulting in agronomic, economic, and environmental benefits due to the decreased potential for off-site reactive N losses. [ABSTRACT FROM AUTHOR]