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Abstract Ranunculaceae, commonly known as the buttercup family, represents one of the earliest‐diverging lineages among the eudicots and contains many species with horticultural and pharmaceutical importance. However, a widely accepted generic classification for this family remains lacking. In this study, we present, to our knowledge, the most comprehensive phylogenetic analysis of Ranunculaceae (227 species), representing almost all currently recognized genera and generic synonyms to date based on five plastid and nuclear loci. We reconstructed the phylogenetic relationships within Ranunculaceae using likelihood, parsimony, and Bayesian approaches. We used the SOWH test to assess the alternative topologies. Our results indicate that Glaucidioideae is the earliest‐diverging lineage in Ranunculaceae, followed by Hydrastidoideae, and Coptidoideae and Thalictroideae are successive sisters to Ranunculoideae. The SOWH test rejects Glaucidioideae as sister to Hydrastidoideae. The sister relationship between Thalictroideae and Adonideae of Ranunculoideae is also rejected. Within Ranunculoideae, the monophyly of each of all 10 tribes is strongly supported. The majority of genera of Ranunculaceae are supported as monophyletic except for Anemonastrum , Enemion , and Oxygraphis . The monophyly of each of these three genera is also rejected by the SOWH tests. Paroxygraphis was included in a molecular phylogenetic analysis for the first time and was nested in Oxygraphis . Based on the results of our molecular data analyses, as well as the results of previous studies, a new subfamilial, tribal, and generic classification of Ranunculaceae is proposed, in which 5 subfamilies, 14 tribes (including one newly described tribe), and 58 genera (including three newly described genera) are recognized.