The aim of this study was to assess whether the nine months of cytostatic inhibition by crystalline sirolimus has a beneficial effect in the two-year follow-up in an all-comer population undergoing percutaneous coronary intervention. The DESSOLVE III study (n=1,398) is a prospective, all-comer, multicentre, randomised controlled study (NCT02385279) allocating 703 patients to receive the MiStent drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall, and 695 patients to receive the XIENCE durable polymer everolimus-eluting stent. At two years, the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction [TV-MI], and clinically indicated target lesion revascularisation [TLR]) occurred in 8.7% and 8.6% (p=0.958) of patients, and the patient-oriented composite endpoint (all deaths, all MI, and all revascularisations) was observed in 18.5% and 19.6% (p=0.598) of patients in the MiStent and XIENCE arms, respectively. The frequency of TV-MI and clinically indicated TLR was also comparable for both stent types. The rate of definite/probable stent thrombosis was not different in the two arms (0.9% vs 1.3%, p=0.435). In an all-comer population, at two-year follow-up, the use of the MiStent sirolimus-eluting bioabsorbable polymer-coated stent was at least as safe and efficacious as the XIENCE durable polymer stent. The MiStent's potential long-term clinical benefit will be further elucidated after five years of follow-up.