The most common side effects of raloxifene are diarrhea, nausea, headache, hot flashes, sinusitis, weight gain, muscle pain, leg cramps, and ankle swelling. Raloxifene may increase blood triglyceride levels in some individuals Raloxifene increases the risk of blood clots, including stroke, deep vein thrombosis (DVT), and pulmonary embolism (blood clots in the lung). The greatest increase in risk occurs during the first 4 months of use. Patients taking raloxifene should avoid prolonged periods of restricted movement during travel when blood clots are more prone to occur. Patients should move around periodically during long trips.

Cholestyramine (Questran) reduces the absorption of raloxifene. Therefore, these two medications should be taken several hours apart. Raloxifene may slightly reduce the ability of blood to clot and thus increase the effects of medications that reduce clotting (blood thinners). Therefore, if raloxifene is given with blood thinners such as warfarin (Coumadin), the ability of blood to clot may need to be monitored more closely with frequent measurements of the prothrombin time of blood.