Patients have received calls from the privately-run hospital telling them not to come in for appointments.
Officers were called just after midnight to Birkby Hall Road, and said a "targeted attack" had taken place.
A local resident, who lives just half a mile away from the hospital, claims he heard '"shotgun noises" last night at around 7.15pm.
He said: “I heard shotgun noises last night.
"We were sat out in the garden around 7.15[pm] and there was two or three shots which were different to any fireworks I’ve ever seen.”
West Yorkshire Police have said there is no suggestion of firearms involvement.
A spokesman for BMI said: “We can confirm that the hospital is temporarily closed while the police investigate an incident which took place outside the hospital.
"We hope to reopen again tomorrow and have been in touch with patients who were due to attend.”
Police received a number of reports from 12.02am.
While officers were en-route to the scene, police were made aware that a man with a number of injuries had arrived at Huddersfield Royal Infirmary.
The man remains in hospital where he is being treated for non-life threatening injuries to his hand. A police scene is in place in a car park of the BMI hospital.
Detective Inspector Mark Atkinson, of Kirklees District CID, said: “Our enquiries are in their early stages but it appears that this was a targeted attack. Neighbourhood officers will be carrying out reassurance patrols in the area.
“We would like to hear from anyone with information about the circumstances of what has happened or those involved.”
Anyone with information about this incident is asked to call Kirklees District CID via 101, quoting crime reference 13180417259. Information can also be given via the 101 Live Chat facility on the West Yorkshire Police website.