Aims and background: Acute poisoning is one of the most common emergencies in India and around the world. Understanding the factors associated with mortality can aid us in devising appropriate preventive strategies to curtail deaths due to poisoning. Purpose of this study is to find various factors that determine the mortality among acute poisoning cases admitted in a tertiary care center. Materials and methods: A retrospective hospital records-based study was conducted at Chengalpattu Medical College Hospital. The study included 2,123 cases of various poisoning cases admitted for a year from January to December 2022. Cases of bites, stings, drowning, and hanging were excluded. Information on sociodemographic profile, type of poison, time since ingestion and admission, and treatment outcome were collected using a structured pro forma. Results: The mean age of the study population was 29.90 ± 14.98 years. Poisoning was found to be predominantly among males (56.42%) and residents of rural areas (58%). Insecticide consumption (27.0%) was the most common modality, followed by oleander poisoning (20%), corrosive poison (17%), rat poison (15%), tablet poison (13%), and other poisons. The overall case fatality rate (CFR) was 5.2%, with the highest CFR of 12.25% with insecticide poisoning. In multivariate analysis, Glasgow coma scale (GCS) score at admission is the only parameter showing a statistically significant association with mortality (adjusted odds-ratio 0.271(0.2–0.38, p-value < 0.01). Conclusion: Acute poisoning primarily affects the young and economically productive population. In the south Indian population, pesticides are still the major contributor though corrosives are a major contributor among children. Mortality is still significant, and GCS status admission is the only predictor of mortality.