The necessity of polymers on drug-eluting stent (DES) platforms is dictated by the need of an adequate amount and optimal release kinetic of the antiproliferative drugs for achieving ideal DES performance. However, the chronic vessel wall inflammation related to permanent polymer persistence after the drug has been eluted might trigger late restenosis and stent thrombosis. Biodegradable polymers have the potential to avoid these adverse events. A variety of biodegradable polymer DES platforms have been clinically tested, showing equal outcomes with the standard-bearer permanent polymer DES within the first year of implantation. At longer-term follow-up, promising lower rates of stent thrombosis have been observed with the early generation biodegradable polymer DES platforms compared to first-generation DES. Whether this safety benefit still persists with newer biodegradable polymer DES generations against second-generation permanent polymer DES needs to be explored.