Thrombo-prophylaxis has been shown to reduce the incidence of pulmonary embolism (PE) and mortality in surgical patients. The purpose of this review is to find out the evidence-based clinical practice criteria of deep vein thrombosis (DVT) prophylaxis in acutely ill medical and critically ill patients. English-language randomized controlled trials, systematic reviews, and meta-analysis were included if they provided clinical outcomes and evaluated therapy with low-dose heparin or related agents compared with placebo, no treatment, or other active prophylaxis in the critically ill and medically ill population. For the same, we searched MEDLINE, PUBMED, Cochrane Library, and Google Scholar. In acutely ill medical patients on the basis of meta-analysis by Lederle et al. (40 trials) and LIFENOX study, heparin prophylaxis had no significant effect on mortality. The prophylaxis may have reduced PE in acutely ill medical patients, but led to more bleeding events, thus resulting in no net benefit. In critically ill patients, results of meta-analysis by Alhazzani et al. and PROTECT Trial indicate that any heparin prophylaxis compared with placebo reduces the rate of DVT and PE, but not symptomatic DVT. Major bleeding risk and mortality rates were similar. On the basis of MAGELLAN trial and EINSTEIN program, rivaroxaban offers a single-drug approach to the short-term and continued treatment of venous thrombosis. Aspirin has been used as antiplatelet agent, but when the data from two trials the ASPIRE and WARFASA study were pooled, there was a 32% reduction in the rate of recurrence of venous thrombo-embolism and a 34% reduction in the rate of major vascular events.