Emergency services, including police, ambulance and fire crew rushed to the Scottish Gas offices on Waterfront Avenue, Granton, after 5pm on Friday.
The police have yet to establish the cause of the incident, but have said it may be chemical in nature.
Police have said that three people were taken to hospital and a further ten others were treated on the scene for minor illness.
The local area has been cordoned off.
Photographs from the scene showed multiple ambulance and fire units in attendance.
An eyewitness told the Evening News that they understood the building had been completely evacuated by around 5.30pm.
Waterfront Avenue and Waterfront Broadway are currently closed in both directions with bus services diverted.
Lothian Buses services 47, X47, 24, 38 and 113 are affected until further notice.
A Police Scotland spokesperson said: “We received a report of a possible chemical incident within a Scottish Gas building in Waterfront Avenue, Edinburgh, around 5.15pm today.
“We are working alongside our partners in the Scottish Fire and Rescue Service to establish the cause of this incident.
“Thirteen people have received treatment at the scene for minor illness. Three of these people have been taken to hospital for further observation.
“We would urge people to avoid the Waterfront area while the emergency response is ongoing.
“Waterfront Broadway, Waterfront Avenue, and Caroline Park Avenue are currently closed and the area is cordoned off.”
A spokesperson for the Scottish Fire and Rescue Service said fire crew were called to the scene at 5.14pm to assist their emergency partners.
Staff were said to be in shock but left in the dark as to the circumstances.
The building at Waterfront Avenue has a staff capacity of 1,150 people.
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