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Rice-wheat cropping system (RWCS), a lifeline for the majority of the population in South Asia is under stress, due to the imbalanced and indiscriminate use of fertilizers. Therefore, we conducted an on-farm study at eight locations (Amritsar, Katni, Nainital, Samba, Pakur, Kanpur, Ambedkarnagar, and Dindori) covering five agro climatic zones of six Indian states (Jammu and Kashmir, Punjab, Uttarakhand, Uttar Pradesh, Madhya Pradesh, and Jharkhand) to (i) calculate the partial factor productivity (PFP) and agronomic use efficiency (AUE) to judge the response of NPK and Zn on grain yield of rice and wheat in RWCS and (ii) to work out the economic feasibility of different combinations of NPK in rice and wheat. Seven fertilizer treatments: Control (0-0-0), N alone (N-0-0), NP (N-P-0), NK (N-0-K), NPK (N-P-K), NPK+Zn (N-P-K-Zn), and FFMP (Farmers Fertilizer Management Practice) were assigned to all the locations. The levels of applied nutrients were used as per the standard recommendation of the location. The average of all the locations showed that the use of NP enhances the grain yield of rice and wheat by 105% and 97% over control, respectively. System productivity of RWCS was expressed in terms of rice grain equivalent yield (RGEY), Mg ha1. Among the locations, Samba recorded the lowest productivity of RWCS with fertilizer treatments. In contrast, the highest productivity of RWCS with fertilizer treatments was recorded at Amritsar, except with NPK and NPK+Zn fertilization, where Katni superseded the Amritsar. An approximately 3-fold productivity gain in RWCS was recorded with the conjoint use of NP over control across the locations. Overall, the results of our study showed that the balance application of NPK increased the productivity of RWCS 245% over control. Partial factor productivity of Nitrogen (PFPn) N alone in rice varied across locations and ranged from 19 kg grain kg1 N at Pakur to 41 kg grain kg1 N at Amritsar. PFPn of N alone in wheat also ranged from 15.5 kg grain kg1 of N at Ambedkarnagar to 28 kg grain kg1 N at Amritsar. However, across locations the mean value of PFPn of N alone was 29 kg grain kg1 N in rice and 21 kg grain kg1 N in wheat. PFPn increased when combined application of N and P sorted in both rice and wheat across the locations. Similarly, combined application of NPK increased partial factor productivity of applied phosphorus (PFPp) in both the crops at all the locations. The combined application of NPK increased the PFPk for applied K at all the location. The response of K application with N and P when averaged over the location was 114% in rice and 93% in wheat over the combined use of N and K. In our study, irrespective of fertilizer treatments, the agronomic use efficiency of applied N (AUEn) and agronomic use efficiency of applied P (AUEp) were greater in rice than in wheat across the location. With regards to the economics, the mean net monetary returns among the fertilizers treatments was minimum (INR 29.5 103 ha1) for the application of N alone and maximum (INR 8.65 103 ha1) for application of NPK+Zn. The mean marginal returns across the locations was in order of N alone > NK > FFM > NPK > NP > NPK+Zn.Not Availabl