So many drugs are available in medicine market with promise to treat the problem of Overactive Bladder (OAB). Among all the drugs Solifenacin and Duloxetine are mostly prescribed by the physicians to treat the above problem. In this work, we compared the treatments by Solifenacin alone versus Solifenacin with Duloxetine with respect to efficacy, better safety profile and positive impact on quality of life in patients of OAB. This was an open, parallel, prospective and randomized trial and was carried out in outpatient of the Department of Medicine, Era’s Lucknow Medical College & Hospital, Lucknow, India and Department of Urology of Chatrapati Shahuji Maharaj Medical university (CSMMU) Lucknow, India. This study may be a very good reference for the medical students, researchers, teachers, scientists as well as the patients and may also be helpful in eradication of the overactive bladder problem which cause the risk of bladder cancer.