Tramadol was complexed with a sulfonic acid cation-exchange resin by a column method. Microencapsulation of tramadol-resin complexes (TRC) was carried out by the spray-drying method. The effect of ethylcellulose (EC) of various viscosities, different solvent systems and addition of plasticizers on microencapsulation were investigated. The morphology of microcapsules was characterized by scanning electron microscopy (SEM). Selected solvents having similar toxicity levels while various physico-chemical properties resulted in greatly different microcapsules. Regular particle morphology and sustained-release behavior were obtained when dichloromethane or ethyl acetate was used as the solvent system, whereas ethanol produced a substantial number of coalesced microcapsules and acetone produced apparently surface-smooth monomicrocapsules with faster release behavior. Three kinds of plasticizers affected the drug release rate similarly. On the addition of plasticizer (DEP), the drug release rate from the microcapsule obtained from low viscosity-grade EC reduced, while there was no alternation for those obtained from middle viscosity-grade EC. Compared to EC with a viscosity of 100 cP, which produced multi-microcapsules and released 60% of the drug within 1 h, microcapsules prepared with 10, 20 and 45 cP viscosity-grade EC showed slower drug release and regular and smooth morphology.