Academic performance of medical students is affected by multiple factors, including cognitive and non cognitive factors. The purpose of this study was to identify the prediction power of selected psychological variables’ (academic self-efficacy and achievement motivation) and students’ previous academic achievement (preparatory grade point average and Ethiopian University Entrance Examination) on medical students’ first year first semester grade point average in Addis Ababa University. The ability of each of these variables in predicting males’ and females’ academic performance was also assessed. The subjects of this study were 227(male = 143 and female = 84) students who enrolled in Addis Ababa University School of Medicine in 2013/2014 academic year. Students’ previous academic achievement and University grade point average (UGPA) were secured from the under graduate Program Office School of Medicine. Academic self-efficacy scale of Pintrich and DeGroot (1990) and Roeser et al. (1996) which were adapted by Mulugeta (1998) and an adapted Academic Achievement Motivation Self- Report Inventory of Daniel (1992) were used to measure participants’ academic self-efficacy and achievement motivation respectively. Data were analyzed using multiple regression analysis. Multiple regression analysis revealed that the predictor variables (preparatory school grade point average, Ethiopian university entrance examination, academic self-efficacy and achievement motivation) added significantly to the prediction of university grade point average (F(4,222)=41.92 ,P<.05),accounting for 43% of the variance in university grade point average of first semester. The regression analyses revealed that a model involving in preparatory grade point average, Ethiopian university entrance examination, Academic self-efficacy and academic achievement motivation on university grade point average was statistically significant for females (F (4, 79) = 14.54, P < .05), accounting for 42% and for male (F (4,138) = 19.6, P < .05), accounting for 36% of the variance in university grade point average. Academic achievement motivation independently did not significantly contribute in predicting males’ and females’ university grade point average sub groups. Practical implication of these findings to the medical school in particular and educational practice in general was discussed. In addition, directions for future research were recommended.