Upon release, the film was the highest-grossing film in its opening weekend in India and had the highest opening day collections for an Indian film up until that point. It also held the record for the highest net collections in the first week for a Bollywood film.
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The film deals with the lives of the 3 friends, whose elation on making it to one of the best engineering colleges in India is quickly deflated by the rigor and monotony of the academic work. Most of the book deals with the numerous attempts by the trio to cope with and/or beat the system as well as Rancho's fling with Pia who just happens to be the daughter of Dr Viru, the domineering head of the Mechanical Engineering Department of their college.
- Aamir Khan as Ranchoddas "Rancho" Shamaldas Chanchad / Chhote / Phunsukh Wangdu, one of the title group of three friends in the engineering college. He went missing after graduation and after 10 years his two friends traveled across India looking for him, while telling stories of their time in engineering college together. Rancho, as a student, was conspicuously ingenious and angry at the inhumanity of the school system. At the end of the film, he is shown to be a famous scientist, entrepreneur and business magnate who also teaches young children when he takes a break from researching.
- R. Madhavan as Farhan Qureshi, the film's narrator and a friend of Rancho and Raju. His father wanted him to be an engineer, but his dream career is wildlife photography; in the end he is shown to have published several books of photographs.
- Sharman Joshi as Raju Rastogi. He comes from an impoverished family with a mother who is a retired school teacher and a paralyzed father who had been a postman. In the flashback story, his family is poor so they can't afford the car that would be demanded as a dowry for his sister. In the present story, he is a settled married man in Delhi who has freed his family from poverty by becoming a wealthy executive.
- Kareena Kapoor as Pia Sahastrabuddhe, Virus' younger daughter, an intelligent and capable doctor. Despite her father's disapproval, she and Rancho fall in love.
- Boman Irani as Dr Viru Sahastrabuddhe (nicknamed Virus), college's strict director. He is also Pia's father, and the film's antagonist. He stubbornly sticks to a doctrinal method of teaching, putting him at odds with Rancho.
- Omi Vaidya as Chatur Ramalingam, a rival student. When he arrives at ICE his Hindi is weak, because he was born in Uganda and educated in Pondicherry, a Tamil-speaking city. He is nicknamed Silencer because the pills he takes, to enhance his ability to memorise passages from textbooks, make him gassy. In the present story, he is vice-president of an American company who only discovers his success being overshadowed by Rancho in the end of the film.
- Rahul Kumar as young Manmohan (nicknamed Millimetre), and Dushyant Wagh as adult Manmohan. As an adolescent, he earns a small living by doing errands for students, such as ironing their clothes, finishing assignments, and getting groceries. Rancho persuades him to buy a school uniform and sneak into school to gain an education. Later he becomes an assistant to Rancho/Phunsukh Wangdu in Ladakh.
- Mona Singh as Mona Sahastrabuddhe, Pia's elder sister and Virus's first daughter.
- Parikshit Sahni as Mr Qureshi, Farhan's father, a strict but loving parent who just wants his son to be happy.
- Farida Dadi as Mrs Qureshi, Farhan's mother, a loving and caring parent.
- Amardeep Jha as Mrs Rastogi, Raju's mother, a retired schoolteacher and dedicated mother.
- Javed Jaffrey as the real Ranchoddas Shamaldas Chanchad. Raju and Farhan go to his home and learn the truth: that Chanchad's father sponsored an orphaned servant boy called 'Chhote', who had demonstrated his intelligence and love of learning, to earn a degree in his name, while the real Ranchoddas was in London. He does appreciate what Chhote did for him, and tells Raju and Farhan where to find him.
- Arun Bali as Shamaldas Chanchad, father of Ranchoddas Shamaldas Chanchad.
- Ali Fazal as Joy Lobo, a student with a passion for machines.
- Akhil Mishra as Librarian Dubey
- Rohitash Gaud as Ranchoddas' servant
- Achyut Potdar as Machine Class Professor
- Madhav Vaze as Joy Lobo's father
- Olivier Sanjay Lafont as Suhas Tandon, Pia's ex-fiance, who cares only about money and ostentation.
- Jayant Kripalani as a company head who conducts Raju's job interview.
- Shameer Ab as a student
- Pooja Goswami as Air Hostess