BACKGROUND: Tempamine is one of new class of antioxidant agents, the nitroxides, which have shown a wide range of biological effects like suppressing free radical driven reactions to maintain cell functions. The objectives of this study were to evaluate the effect of a biodegradable polymer coated stent loaded with tempamine on in-stent neointimal formation. METHODS: Stainless steel stents were dip coated in biodegradable elastomeric poly (ester-amide) (co-PEA) or in polymer solution mixed with 50% (wt%) and 100% (wt%) tempamine. One group 100% (wt%) tempamine loaded stents were further dip coated in co-PEA polymer to form a top layer. Stainless steel bare, polymer-only, and different doses tempanine coated stents were implanted into porcine coronary arteries with a stent to artery ratio 1.2:1. Histomorphometric analysis was performed at 5 days and 6 weeks respectively. RESULTS: Histomorphometric analysis showed that the bare, polymer-only and tempamine-coated stents elicited a similar tissue response at 5 days. At 6 weeks, the peri-strut inflammation and neointimal hyperplasia of polymer-only stents were comparable to the bare stents. Compared to the bare stents, 50% tempanine coated stents had a trend to decrease the arterial injury (0.62 +/- 0.41 versus 0.34 +/- 0.18, P = 0.075) and neointimal hyperplasia (1.80 +/- 0.77 versus 1.27 +/- 0.39 mm2, P = 0.085). However, 100% tempanine coated showed significantly increased inflammatory response and neointimal formation. CONCLUSION: These co-PEA polymer coatings showed a biocompatible performance. Loaded with 50% tempamine had a trend to decrease neointimal hyperplasia. The 100% tempamine for stent-based delivery may have potential cytotoxic effects to arterial wall. Using a co-PEA polymer topcoat could effectively abolish these side effects.