Upper extremity deep vein thrombosis (UEDVT), which has a different cause than lower limb DVT, frequently results from the use of a catheter, cancer, or thoracic outlet syndrome. Direct oral anticoagulants (DOACs) are approved for the treatment of lower limb DVT, but their effectiveness in UEDVT has not been thoroughly investigated. This meta-analysis assesses the effectiveness and safety of DOACs in UEDVT in comparison to low-molecular-weight heparin (LMWH). Nine studies with 643 patients treated with DOACs were found through a methodical search of PubMed. Mortality, the recurrence of venous thromboembolism (VTE), pulmonary embolism (PE), and significant bleeding were the outcomes. When compared to historical LMWH data, DOACs showed significantly reduced mortality (2.49 vs. 16.5−27.5; p\<0.001%), VTE recurrence (0.93 vs. 5; p\<0.001%), and PE incidence (0.31 vs. 5−8; p\<0.001%). With DOACs, however, the rates of major bleeding were greater (2.02 vs. 0.25; p\<0.001%). Rivaroxaban was the most frequently prescribed DOAC (70.9) in patient groups with UEDVT that was primarily cancer-related (66.7) or catheter-associated (64.5). The median length of treatment was three months, and there was a six-month follow-up period. These results imply that DOACs may be more effective at lowering mortality and thrombotic events in UEDVT, but they also carry a higher risk of bleeding. The study's limitations include its reliance on historical LMWH comparisons, the variety of study designs, and the low number of PE occurrences. To evaluate long-term results, standardized imaging and longer follow-up are required. Although DOACs are a viable option, care should be taken when prescribing them to individuals who are at a high risk of bleeding. To confirm these findings and improve clinical recommendations, more randomized trials are required.