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This study investigated the effectiveness of using metacognitive prompts during testing for improving results in a Genetics Problem Solving Test (GPST). The study, a pre-test post-test, control group quasi-experimental design involving 2x2x2 analysis of covariance (ANCOVA) also investigated the moderating effects of gender and school type. A total of 2,138 high school students purposively selected from seventeen high schools in Western province, Kenya, participated in the study using three validated instruments; Biology Ability Test (BAT), Genetics Problem Solving Test (GPST), and Metacognitive Prompting Questionnaire (MPQ). Findings showed that metacognitive prompting (MP) had a significant effect on students’ genetics problem solving ability, F(1, 2137) = 10.909, p < 0.001. The findings also revealed gender differences, with girls outperforming boys on the genetics problem solving test. Furthermore, a significant interaction between metacognitive prompting and school type showed that students in provincial schools benefited from MPs more than students from district schools. This study established a foundation for instructional methods for biology teachers and recommendations are made for implementing metacognitive prompting in a problem-based learning environment in high schools and science teacher education programs in Kenya.