Background: The ultrathin-strut bioresorbable-polymer sirolimus-eluting stent (BP-SES) demonstrated comparable performance to durable-polymer everolimus-eluting stent (DP-EES) in randomized controlled trials. The purpose of this study was to evaluate the performance of a BP-SES compared with a DP-EES in calcified or small vessel lesions, which represent higher risk of restenosis. Methods: From the pooled BIOFLOW (BIOFLOW-II, IV, and V; BIOTRONIK - A Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects With up to Three De Novo or Restenotic Coronary Artery Lesions ) randomized controlled trials, a total of 1553 BP-SES and 784 DP-EES patients with valid 1-year follow-up data were available. Coronary lesions were assessed for the presence of moderate-to-severe calcification or small vessels (reference vessel diameter, ≤2.75 mm) by core laboratory analysis. One-year clinical outcomes were assessed with or without the lesion subsets between BP-SES and DP-EES. Results: Baseline characteristics were similar between the groups. Among patients with small vessel disease, target lesion failure (8.0% versus 12.4%; P <0.01) and target vessel myocardial infarction (4.2% versus 7.6%; P <0.01) were significantly lower in BP-SES than in DP-EES. No difference in the outcome between the stents was shown in patients with non-small vessel lesions. In patients with calcified lesions, target lesion failure (12.2% versus 6.9%; P =0.056), and cardiac death (1.9% versus 0.3%; P =0.081) were numerically higher in DP-EES than in BP-SES. In the noncalcified lesion analysis, target vessel myocardial infarction in DP-EES was significantly higher than in BP-SES. Stent thrombosis was similar between the stents in both lesion groups. Conclusions: Among patients with more complex disease representing a higher risk of target lesion failure, the effectiveness of an ultrathin-strut BP-SES compared with a thin-strut DP-EES was maintained through 1 year. Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01356888, NCT01939249, NCT02389946.