Background: Students enter the medical study with internally generated motives like genuine interest (intrinsic motivation) and/or externally generated motives like parental pressure or desire for status or prestige. Due to limited information available on the motivational factors to take up medicine among Indian students, this study was carried out to determine motivations of first-year medical students’ towards a medical career. Methodology: This cross-sectional study was carried out among all 250 first year medical students of Kasturba Medical College (Manipal University), Mangalore in February 2015. Data collection was done using a pre-tested semi structured questionnaire, consisting of 16 questions about demographic and academic characteristics; motivational factors to study medicine; and the role of career guidance in choice of study Data were analysed using SPSS (Statistical Package for Social Sciences) version 11.5. Results: Of 250 students, 246 (98.4%) submitted completed questionnaires. The majority of the students (72%) were self-motivated for choosing medicine as a career; 64.2% chose medicine because it is a humane and noble profession; 50.4% for respect and prestige it provides; 36.6% were inspired by the family; 27.2% because of the non-requirement to study Mathematics and Physics and 14.6% for financial security. Also, 16.3% students had parents in the medical profession; Fifty-seven students (55%) got admission after > or = 2 attempts; 46% decided on a medical career before class ten. Overall, 13% had sought career counselling. More than half of the students had accurate knowledge about the curriculum, course duration, examinations, and post graduate training. Conclusion: Nobility of the profession, prestige, and inspiration from family members were the predominant motivating factors. Determining the reasons for choosing medicine has important implications for the selection and training of students as well as for their future job satisfaction.