The aim of this study was to determine the diversity and structure of aquatic macroinvertebrates in the middle course of the Comoé River. Sampling of macroinvertebrates was carried out at four stations in this course. A total of 3921 individuals of aquatic macroinvertebrates were identified in this part of the river. These macroinvertebrates are divided into 137 taxa, 72 families, 17 orders and 6 classes. Insects with 64% numerically dominate this population of aquatic invertebrates. They are followed by gastropods (21%). Ephemeroptera (27%), Mesogastropoda (21%) and Coleoptera (13%) are the most abundant orders. The most diverse orders are Coleoptera (27 taxa) followed by Ephemeroptera (19 taxa). The Dytiscidae (8 taxa) constitute the most diversified family in this part of the river. According to the number of individuals per species, Melanoides tuberculata (8%) dominates in the middle course. In the middle course, the Shannon-Weaver index varies from 2.85 to 3.56 and the fairness from 0.83 to 0.95. The abundance coupled with the various indices of diversity studied reveal that the waters of the stations of the middle course are well populated in aquatic macroinvertebrates and well diversified.