Three men are in a critical condition after a fire broke out at an Adelaide hotel, with police investigating if the blaze was suspicious.

Seven people were hospitalised after the fire, which started at 6.30am at the Comfort Hotel Adelaide Meridien in Melbourne St, North Adelaide.

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Flames can be seen coming from hotel windows in footage shot from the street, with witnesses saying screams rang out.

Many terrified guests managed to get out, but around 15 people, some stuck on balconies, were rescued from the building by Fire and Rescue crews, using ladders and cherry pickers.

Carli Leishman said she saw a hotel room engulfed in flames.

"As we were going down the stairs we actually could see the room that was on fire and you could hear them screaming 'help! help!'" she said.

One man, who suffered serious burns, jumped into the hotel's pool before authorities arrived.

A ladder came to the rescue of Isla Whitfield and her family.

They'd just helped a line of terrified guests who'd been crawling blindly through the darkness, unsure of where an exit was.

Hotel Darren Whitfield said he called out to help.

"I called out to them to crawl, make sure you stay low, and out of the smoke comes these people and they have soot all over their faces, all over their body," he said.

A man in a wheelchair had to use the lift to escape.

Chief Inspector Matt Nairne from South Australia Police, said police are investigating the fire in the three-level building.

"There's always the likelihood that you'll end up with a lot more injury or death with a fire of that scale where there's multiple occupancy," he said.

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Guests have since been escorted back into the hotel, with staff working with police to help arrange alternate accommodation.

Anyone with information should contact Crime Stoppers.