Semi-solid poly(ortho esters) (POE) were prepared to provide bioerodible carriers for sustained drug delivery systems of nifedipine in the treatment of cardiovascular disease. As the POE has viscous behavior at room temperature, a significant advantage of this polymer is that it can be injected without any surgical intervention. The POE was synthesized by a transesterification reaction between 1,2,6-hexanetriol and trimethyl orthoacetate and the nifedipine release from POE was studied in vitro. The release rate of nifedipine decreased with increasing the amount of nifedipine and the diethanolamine dispersed in the polymer. But the excess amounts, above 3%, of diethanolamine retarded the release of nifedipine. In vivo biocompatibility studies were carried out in rats with nifedipine loaded POE. Histopathological analysis showed that nifedipine loaded POE implants were well-tolerated by rats when used subcutaneously. In case of the rats implanted POE containing diethanolamine, tissue necrosis and inflammation were occured. Pharmacokinetic studies of nifedipine loaded POE implants were carried out in rabbits. In all cases, plasma concentrations of nifedipine were maintained over 15 ng/ml for at least 360 hours and biological half $life(t_{1/2})$ and mean residence time(MRT) were increased by addition of diethanolamine.