Courses related to medical and engineering fields are quite extensive and demanding, which often lead to stress and anxiety among students. As optimism was hypothesized to reduce anxiety and enhance academic achievement, the purpose of the current study was to assess the level of anxiety and its relation with optimism and academic achievement among medical and engineering students. Since these two courses differ in many aspects and the gender roles in the society are changing, the secondary objective of the study was to find differences in anxiety, optimism and academic achievement across genders and academic majors. A total of 346 students (171 medical and 175 engineering) from 3 medical and 4 engineering colleges of Uttar Pradesh, India participated in the study. Academic results of the latest two semesters were considered as academic achievement of the students, whereas anxiety and optimism were tested using Sinha's Comprehensive Anxiety Test (SCAT, 2007), and Learned Optimism Scale (LOS, 2000) respectively. Both measures are constructed and standardized on Indian students. Results revealed that anxiety had a significant negative relationship with optimism and academic achievement, whereas a significant positive relationship was found between optimism and academic achievement. Significant differences were revealed between medical and engineering students, but the gender differences in the variables under study were insignificant. The results of this study provide insights for faculty members and institutions for better academic performance of the students.