Multiple unit particulate system (MUPS) is more recent, challenging, effective and attractive option for the pharmaceutical industries that gives an efficient way to deliver drugs in modified pattern. This study aimed to improve the release profile of venlafaxine hydrochloride by developing modified release MUPS using polyvinyl pyrrolidone K-30, ethyl cellulose 20 cps and Hypromellose E 5LV. Preliminary trials were carried out to select the inert carrier, binder, and viscosity grade of rate controlling polymers. Further, optimization of binder concentration and extended-release coating was carried out. The formulation development of MUPS was divided into two categories as (i) drug layering on inert carrier, i.e., sugar spheres and (ii) extended-release coating. Comparative multimedia dissolution study of venlafaxine hydrochloride extended-release capsules was carried out and compared with the marketed formulation to ascertain the in vitro drug release behavior. XRD study indicated conversion of monohydrate form of venlafaxine hydrochloride and remained unaffected during storage. SEM images confirmed smooth surface of MUPS without any pores. The coated spheres had more dense surface compared to the uncoated pellets. Hypromellose E 5 LV showed better binding properties. Ethyl cellulose (20 cps) showed sustained release profile. The blend containing ER -I spheres (10% coating) and ER -II spheres (11% coating) at 60: 40 ratio showed dissolution profile similar to that of the innovator product. The formulated venlafaxine hydrochloride loaded MUPS filled in hard gelatin capsule can open a new avenue for the delivery of therapeutics with improved potential.