Aim: This study aimed to examine the histopathological effects of acetaminophen (ACMP) abuse in select organs of male Wistar rats. The second goal was aimed at determining the prevalence of ACMP abuse in human subjects.Materials and Methods: A cross‑sectional design (structured questionnaire and oral interview) was used for data collection from 1911 male to 1009 female subjects, aged (15–72) years in Benin City, Nigeria, between June, 2014 and April, 2015. The animal study was done using 60 adult male Wistar rats with a mean weight of (228.34 g). ACMP was orally administered to 10 Groups of rat in the following order: Groups A1 and A2 (400 mg/kg), B1 and B2 (800 mg/kg), C1 and C2 (1200 mg/kg), and D1 and D2, (1600 mg/kg) body weight in rat. Water and feed were provided ad libitum for the duration of ACMP administration that lasted for 21 days (sub‑acute exposure) in Group A1, B1, C1, and D1 . The administration lasted for 42 days (sub-acute and acute exposures) in Groups A2, B2, C2, and D2 while Groups E1 and E2 served as the control. At termination, all rats were sacrificed by cervical dislocation, grossed, and processed histologically.Results: The prevalence of ACMP abuse within the study population (males and females, in Benin City, Nigeria) stood at 97.3% and was significantly affected by contributory factors like: Age‑group, income, profession, etc. Grossly, renal and hepatic necrosis was observed in the high‑dose/acutely exposed treated rats (C2 and D2). Histopathology findings revealed hepatocellular distortion at the central vein of the liver tissue and tubular expansion and increased glomerular space in the kidney. Decrease in body weights of the rats in Groups C2 and D2 were statistically significant (P < 0.05).Conclusion: There was a high incidence of ACMP abuse in the males and females population in Benin City, Nigeria. Prolonged oral consumption of ACMP in animals resulted in hepatocellular and renal deleterious effects and may be of a similar hazard in humans.Keywords: Acetaminophen, cross‑sectional survey, gross examination, histochemical methods, histological technique