Recently, nanotechnology applications have increased tremendously in consumer products. However, it has been observed that these nanoparticles can cause a potential risk to the environment as well as human health. In the present manuscript, we have analyzed acute and sub-chronic toxicity of engineered silver nanoparticles (AgNPs) by assessing the impact on Wistar rats. AgNPs were synthesized by a novel approach—thermal co-reduction—with spherical shape and a uniform size distribution of 60 nm. The estimated LD50 value was observed to be more than 2000 mg/kg bw in acute toxicity studies. Sub-chronic toxicity indicated impairment of liver and kidney enzymes and various hematological and biochemical parameters. Tissue distribution studies indicated the target organ for accumulation is liver after treatment with AgNP. Particle deposition and congestion was observed in major organs-though, and heart and pancreatic tissues were not affected even by the higher doses. On the basis of the observations of this study, it is concluded that up to 40 mg/kgbw is a safer dose of AgNPs (60 nm, engineered by thermal co-reduction approach) and further research will be required to validate the long-term accumulation in body. In addition, it can also be considered by policymakers for the safer use of AgNPs. © 2019, King Abdulaziz City for Science and Technology.