Background: The participation and performance of females at school is lower besides higher dropout rate due to numerous factors. Primary dysmenorrhea is one of the most apparent gynecologic complaints of females beginning in adolescence and causing class absence. However, there are very few data on association of primary dysmenorrhea and academic performance at all levels of educational institutions, particularly in secondary schools, of Amhara Region. Objective: To determine the association between primary dysmenorrhea and academic performance of students age 13-19 years at Woreta secondary school, North west Ethiopia. Method: Institution based cross-sectional study was employed in October 2018. A total of 430 female students were selected using simple random sampling technique. A pretested self-administered questionnaire was used to collect the data. The coded data was checked and cleaned using Epi Info version 7 and exported to SPSS version 20 for analysis. Simple and multiple linear regression analyses were applied. ANOVA statistic was used whether the model used fit or not with p-value ≤ 0.05. Result: In this study, a total of 430 female students were included. All participants filled the provided questionnaires. Three hundred twenty-four, 75.3% of the students had primary dysmenorrhea. Primary dysmenorrhea, class concentration, perceived fear of low academic performance, live with both parents, and live with only mother were significant predictive of academic performance [F (5,424) = 38.226, p<0.001]. Primary dysmenorrhea was found to be contributed the biggest (beta = -11.493) followed by perceived fear of low academic performance (beta = -4.855), live with both families (beta = -3.089), live with only mother (beta = -3.504), and class concentration (beta = -1.856) respectively on student semester average score. Conclusion: Primary dysmenorrhea, perceived fear of low academic performance, living with both parents, living with mother, and perceived loss of concentration were significantly predictive of average score of female students in secondary school. Keywords: Female student, Semester average, Secondary school