In January 2011, Rajinikanth was slated to appear in Rana, a period film to be produced by Soundarya Rajinikanth and directed by K. S. Ravikumar, who would work with the actor for a third time. During the principal photography of the film on 29 April 2011, he suffered a mild foodborne illness on the sets, which led to vomiting, dehydration, and exhaustion. He was treated at St. Isabel's Hospital for a day before being discharged. Five days later, he was rushed to the same hospital again after suffering from breathlessness and fever. He was diagnosed with bronchitis and was kept at the hospital for a week, while also spending a few days in an intensive care unit. Several conflicting reports of discharge dates arose, as well as claims of Rajinikanth's health deteriorating. Two days after his last discharge, Rajinikanth was admitted to the Sri Ramachandra Medical College and Research Institute on 16 May 2011 for recurring respiratory and gastrointestinal problems. The hospital maintained that Rajinikanth was in stable condition and showed positive response to treatment. It was widely reported that he required a kidney transplantation, which was later denied by Dhanush.
On 21 May 2011, Aishwarya Rajinikanth released a photo of her and Rajinikanth in his hospital ward, both posing with a thumbs signal, responding to fans' negative reaction to news reports. The hospital restricted unauthorised visitors. Rajinikanth's brother, Sathyanarayana Rao Gaekwad, reported that the cause of the sudden illness was due to stress from rapid weight-loss and changes in diet, as well as withdrawal of alcohol consumption and smoking cessation. After addressing fans in a 4-minute digitally recorded voice message to the media, Rajinikanth, under the advice of Amitabh Bachchan, travelled from Chennai to Singapore with his family on 21 May 2011, where he was to undergo further treatment for nephropathy at Mount Elizabeth Hospital. After spending over two weeks at the hospital, he was finally discharged on 15 June 2011 and continued to recuperate in Singapore, before returning to Chennai on 13 July 2011.
Despite several failed attempts to restart Rana upon his return, Rajinikanth reprised his Enthiran character, Chitti, in the Bollywood science-fiction film Ra.One (2011) in a guest appearance alongside Shah Rukh Khan and Kareena Kapoor. In November 2011, it was decided that Rana would be shelved in favour of a new project, titled Kochadaiiyaan. The motion capture film, which is the first of its kind in India, was released in 2014 to positive reviews. Kochadaiiyaan, and the 3D release of Sivaji in 2012, made Rajinikanth the first Indian actor to have appeared in four different forms of world cinema: black-and-white, colour, 3D and motion capture. Following the completion of Kochadaiiyaan, Rajinikanth began work in Ravikumar's next directorial venture, titled Lingaa alongside Anushka Shetty and Sonakshi Sinha. The film was released on 12 December 2014, coinciding with his birthday, and received mixed reviews from critics. Rajinikanth's next film was director Pa. Ranjith's crime drama Kabali, produced by S. Thanu. The film was released in July 2016.
According to Naman Ramachandran, the author of Rajinikanth: The Definitive Biography, most of Rajinikanth's philanthropic activities went unpublicised because he chose to keep them undisclosed. In the 1980s, when superstitious beliefs in Tamil Nadu created a stigma towards eye donation, Rajinikanth took the case of campaigning in support of corneal transplantation via television and public speeches. In 2011, Rajinikanth announced his support for the anti-corruption movement led by Anna Hazare and offered his commercial wedding venue, the Raghavendra Kalyana Mandapam, in Chennai free of cost for the India Against Corruption members to hold their fast. Rajinikanth's fan associations regularly organise blood donation and eye donation camps and distribute food during his birthday.