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Powerpoint Instructional Strategy and Students' Performance and Retention in Biochemistry in Federal Universities, South-South, Nigeria aimed at determining the effect of PowerPoint instructional strategy on students' performance & retention with reference to gender and cognitive ability levels. The quasi-experimental; and pre-test post-test non-randomized control group designs were employed for data collection from 4 selected federal universities in the study area. Instruments used for data collection include Performance Test on Glucose Metabolism (PTGM), Cognitive Ability Test (CAT) and PowerPoint Instructional Package on Glucose Metabolism (PIPGM). The data obtained were analyzed using Analysis of Covariance (ANCOVA) for the entire hypothesis tested at .05 level of significance. The analyses revealed that the use of PowerPoint instructional strategy enhanced Biochemistry students' academic performance and retention more than the use of expository teaching method while glucose metabolism concept taught were not dependent on gender and cognitive ability levels contrary to the sex-role stereotype perpetrated by families, schools and society. Necessary recommendations were made.