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Studies have shown that the continuous application of N, P, and K fertilizers has led to the depletion of secondary and micronutrients, which have become limiting nutrients hindering crop growth and yield. An on-farm trial was conducted to determine the effect of site-specific nutrient fertilizers and compost on soybean yield, phosphorus use efficiency, and soil properties, at Nyong Guma, Serekpere, Daffiama Saapare, and Naaga in northern Ghana. Nine (9) treatments (3 rates of mineral fertilizer × 3 rates of FertiSoil) were applied in a factorial combination arranged in randomized complete block design with three replications. On average, the soybean grain yield increased significantly with the combined application of FertiSoil and mineral fertilizer at full rates at Nyong Guma, Serekpere, and Naaga from <1,000 kg ha⁻¹ to > 1,500 kg ha⁻¹. The co-application of 50% recommended rate (RR) of mineral fertilizer and 5 t ha⁻¹ FertiSoil increased soybean grain yield by over 250% at Daffiama Saapare. The application of 50% RR mineral fertilizer significantly increased phosphorus use efficiency by 5–55% compared to its combination with FertiSoil or FertiSoil alone at different rates across locations. Incorporation of 5 t ha⁻¹ FertiSoil and 100% RR mineral fertilizer significantly increased exchangeable K, Ca, and Mg, and microbial C and P by 0.33, 2.84, 0.56 cmol₍₊₎ kg⁻¹ and 102.7, 33.37 mg kg⁻¹, respectively, at Serekpere. The combined application of 5 t ha⁻¹ FertiSoil and 50% RR mineral fertilizer relatively increased soil organic C (42%) and available P (12%) at Naaga. The soil quality index revealed that the addition of 5 t ha⁻¹ FertiSoil to 100 …