Epidural injection of corticosteroids is a commonly used treatment for radicular pain. However, the benefits are often short lived, and repeated injections are often limited secondary to concerns of side effects from cumulative steroid doses. In addition, rare, catastrophic complications, including brain and spinal cord embolic infarcts have been attributed to particulate steroid injections. A previous study has shown that dexamethasone has less particulate than other corticosteroids, possibly reducing embolic risk. Furthermore, a recent study indicated that clonidine may be useful in the treatment of radicular pain when administered via epidural steroid injection. The combination of corticosteroid and clonidine is an intriguing, yet unstudied, alternative to traditional treatment. Our study examines whether mixing clonidine and various corticosteroids results in increased particle size or aggregation. Evaluations under light microscopy for particle size were made of samples of clonidine alone and clonidine mixed with equal parts of 3 corticosteroids solutions: dexamethasone sodium phosphate injection, triamcinolone acetonide injectable suspension, and betamethasone sodium phosphate and betamethasone acetate injectable suspension. Four mL each of clonidine (100 μcg/mL), clonidine (100 μcg/mL) + dexamethasone sodium phosphate injection (4 mg/mL), clonidine (100 μcg/mL) + triamcinolone acetonide injectable suspension (40 mg/mL), and clonidine (100 μcg/mL) + betamethasone sodium phosphate and betamethasone acetate injectable suspension (6 mg/mL) were examined Their particle sizes were compared to measurements taken when each steroid solution was examined alone. Clonidine was determined to be nonparticulate when examined by light microscopy. Clonidine mixed with equal parts of each of the 3 corticosteroids mentioned above did not result in increased clumping or increased particle size over each of the corticosteroids measured alone. Mixing clonidine with corticosteroids did not increase particulation compared to corticosteroids alone. Combining clonidine and corticosteroids for epidural injection may prove to be a useful treatment for radicular pain. The combination of these is unlikely to result in a solution that is more likely to cause embolic infarcts than the use of corticosteroids alone.