This book constitutes the refereed proceedings of the 12th International Conference of the CLEF Association, CLEF 2021, held virtually in September 2021. The conference has a clear focus on experimental information retrieval with special attention to the challenges of multimodality, multilinguality, and interactive search ranging from unstructured to semi structures and structured data. The 11 full papers presented in this volume were carefully reviewed and selected from 21 submissions. This year, the contributions addressed the following challenges: application of neural methods for entity recognition as well as misinformation detection in the health area, skills extraction in job-match databases, stock market prediction using financial news, and extraction of audio features for podcast retrieval. In addition to this, the volume presents 5 “best of the labs” papers which were reviewed as full paper submissions with the same review criteria. 12 lab overview papers were accepted and represent scientific challenges based on new data sets and real world problems in multimodal and multilingual information access.