To evaluate the effect of Oral-Anticoagulants in Non-Valvular Atrial Fibrillation(NVAF) to control the occurrence of stroke and to assess the mortalityrate, hospital-readmissions, duration of hospital-stay associated with its use in South-Indian population. Methods: This retrospective, comparative hospital-based study conducted in a tertiary-care hospital, Kerala. In this study, NVAF patients with more than eighteen years who were initiated with Newer-Oral-Anticoagulants(NOACs) or Warfarin during the period from January-2016 to January-2018 were selected. Patients with Valvular-Heart-Disease, Transient-Ischemic-Attack, Deep-Vein-Thrombosis, Pulmonary-Embolism, End-Stage-Renal-Disease and those who contraindicated to these drugs were excluded. The patients were followed-up for a period of 1year. The effect of drugs in controlling the occurrence of stroke, stroke-free period, hospital-readmissions, length of hospital-stay and allcause mortality were compared and analyzed among the groups. Analysis of Variance test(ANOVA) were used to compare the baseline parameters and Student's t test, used to compare categorical variables. Results: A total of 133 patients (51warfarin and 82NOAC-group) were enrolled. The number of patients on NOACs had a clinical benefit over warfarin in controlling stroke (78.04% vs 70.58%),(P=0.22). Stroke was not reported in 7.47% of NOAC users during the entire study-period. They were associated with lesser cardiac complications(36.5%), readmissions(15.85%; P=0.07); and had higher risk-reduction in readmissions (41.7%; Relative-Risk-Reduction=0.417) and mortality (12.91%; RRR=0.1291). Mean duration of hospital stay was equally-likely in both groups (Warfarin7;NOACs6). Warfarin-users experienced higher incidence of mortality within first six-months of initiation though mortalityrate similar in both groups during entire study-period (19.6% vs 17.1% for warfarin vs NOAC),[P=0.71]. Hazard ratio were assessed in terms of stroke [0.49 (CI:0.15-1.57);P=0.24), mortality [0.28(CI:0.06-1.19); P=0.71] and major-bleeding [0.844(CI:0.34-2.07);P=0.08] between both drugs, indicating NOACs were associated with lower-risk and had higher safety profile. Conclusions: NOACs were found to be a better alternative for NVAF patients, due to its higher risk-reduction, improved health outcomes and clinical benefits over warfarin under routine clinical settings in South-India.