Aim: Depression is a mental disorder which affects more than 250 million people independently of their age. Venlafaxine is an antidepressant drug and used also for the treatment of panic attack and anxiety with fewer side effects than older antidepressant therapeutics. However, venlafaxine hydrochloride (VH) has a short half-life which requires three times dosing daily to maintain sufficient plasma drug concentration. The aim of this study is to develop sustained release VH tablets to be given once a day. Material and Methods: Polyethylene oxide, sodium alginate, hydroxypropyl methyl cellulose, guar gum and polyacrylic acid were used as controlled release agent. Tablets were prepared by direct compression method. Powder (angle of repose, flow rate, Carr index and Hausner ratio) and tablet (weight uniformity, hardness, friability,) characterizations were evaluated. In vitro release studies were carried out for 24 h and drug release kinetics were evaluated using different models. Results: All formulations showed suitable Carr index and Hausner ratio except the formulation prepared with guar gum. The tablets which had been manufactured via direct compression method were compared to the commercial tablet. Sustained release of VH was observed for all formulations. Based on the in-vitro dissolution studies, the drug release from F1 formulation which comprising HPMC and Carbopol polymers was found similar as compared to the commercial tablets. Conclusion: Directly compressed VH tablets could be a preferable alternative to the commercial tablets on behalf of patient compliance and fewer manufacturing steps compared to other production methods.