In 2000, he starred in the comedy 'Hera Pheri' which showcased his brilliant ability at doing comedy, similar to that of action and romantic roles. He also starred in the romantic film, 'Dhadkan' (2000) later that same year which also earned reasonable takings at the box office.

In 2001, Akshay Kumar played a negative role in the film 'Ajnabee'. Akshay also had critical appreciation for his role as a blind man in 'Aankhen' which was a box office success of that year.

Following the success of 'Hera Pheri', he starred in a number of comedy films, including 'Awara Paagal Deewana' (2002), 'Mujhse Shaadi Karogi' (2004) and 'Garam Masala' (2005). Apart from his action, comedy and romantic roles, Akshay Kumar displayed a flair for dramatic roles in films such as 'Ek Rishtaa' (2001), 'Aankhen' (2002), 'Bewafaa' (2005) and 'Waqt: The Race Against Time' (2005).

In 2006, he starred in a sequel to 'Hera Pheri', titled 'Phir Hera Pheri'. Later that year, Akki starred alongside Salman Khan in the romantic musical, 'Jaan-E-Mann' (2006). He ended the year with the comedy, 'Bhagam Bhag' (2006), which was a success.