Ghosh, who brought back discerning Bengali film audience back to cinema houses, was suffering from pancreatitis. He breathed his last at 7:30 am after a massive heart attack.
Reports said he perhaps had died in sleep hours back.
Ghosh had won several awards in his career including 12 National Awards.
Born in 1963, Ghosh started his career in advertising and his directional debut was a children's film, Hirer Angti (Diamond Ring).
He got National film award for Best Director for his Bengali film "Abohoman".
His last released film was Chitrangada where he also acted essaying the role of a gay dancer.
Rituparno Ghosh was also a gay icon who lived his life in his own terms in recent years, often dressing boldly to boast his effeminate bearing.
Ghosh made films not only in Bengali, but also in Hindi and English and all top Indian actors from Amitabh Bachchan to Sharmila Tagore, Rakhee, Ajay Devgn and Aishwarya Rai expressed happiness to be cast in his projects.
Reacting to his death Trinamool Congress (TMC) Rajya Sabha member Derek O'Brien tweeted: "A friend for 30 yrs. A neighbour. A buddy from our days in advertising. A champ director. My wife's fave Kolkatan. Rituparno Ghosh. Gone to[o] soon."
Bengali actor Dada Saheb Phalke winning Bengali actor Soumitra Chatterjee said: "This is a shocking news. He was a talented filmmaker and perhaps even his full potential was not realised yet. I am shocked, bereaved and yet to come to terms to the news."
Ghosh burst into the Bengali film world with his 1994 film Unishe April and then directed Dahan and went on to make films like Titli, Bariwali, Dosar and The Last Lear starring Amitabh Bachchan and Preity Zinta.
"I still cannot believe it. My daughter was shooting with him only a few days ago," said filmmaker Goutam Ghosh.
He hosted two celebrity chat shows, namely 'Ebong Rituporno' and 'Ghosh and co'.
Ghosh had also made films based on the novels of Rabindranath Tagore, lending his signature treatment to the films.
Bollywood mourns the death
The film fraternity took to Twitter to express their grief over the sudden demise of the film-maker
Madhur Bhandarkar: I'm speechless and shocked to know that talented filmmaker Rituparna Ghosh has expired. I had met Ritu a couple of time, he was a very warm and humorous person. He most definitely will be missed.
Rohit Roy: Just heard about Ritu da. This is unbelievable. Just spoke to him a couple of days back to say I'm coming to Kolkatta for my release. A lot of dreams unfulfilled. Am sure he had so much more to give to cinema. Gone far to early. Rituparno Ghosh-RIP
Manoj Bajpayee: Sad to hear about the passing off a very dynamic talented Rituparno Ghosh.RIP. Will miss you my friend!
Onir: Shocked and still hoping that its not true. Film maker and friend Rituparno Ghosh is no more. Apparently had a massive heart attack.
Kabir Bedi: Stunned by Rituparno Ghosh's tragic passing. A phenomenally creative director! We'd discussed a Tagore project. RIP
Divya Dutta: Shocked to hear about Ritu da! Not sinking in! Fondest memories of working wth him in 'The Last Lear'! RIP
Ranganathan Madhavan: Oh God. Saddened to hear of the untimely demise of a very learned man and one of my directors Rituparno Ghosh. RIP my friend.
Siddharth: Rituparno Ghosh. 49. Gone too soon. Great film maker. Warm, kind person. Terrible tragedy. RIP.
Shoojit Sircar: I am just devastated hearing the news of Rituparno Ghosh
Kunal Kohli: Sad and shocking to hear about Rituparno Ghosh. RIP
Sophie Choudry: Very sad news. RIP Rituparno Ghosh. A wonderful storyteller, filmmaker gone too soon.