The Prince Regent River is a remote tidal estuary on the Kimberley coast, characterized by high cliffs, mangrove-lined shores, and significant tidal influence. Access is extremely remote, typically involving a multi-week coastal paddle from a point like Derby or a boat drop. There are no formal launches or take-outs; paddlers must use natural features like rocky capes or beaches, which can be exposed and slippery at low tide. The tidal range in the broader Kimberley region is among the highest in the world, exceeding 11 meters in places, dictating all travel. Paddlers must plan journeys around these tides, with one account describing a planned 70-kilometer paddle upriver on an incoming tide to reach Camp Creek and a waterfall. The coastline features few landing spots, with long stretches of mangroves or high cliffs, making it critical to reach a known campsite before sunset.

The river and its coastline are exposed and treacherous, with unsettled weather and the potential for cyclones during the wet season. A primary and severe hazard is the presence of a large population of saltwater crocodiles; surveys have historically counted high numbers in the river, and fatal attacks on humans have occurred. The water is murky, and crocodiles can be encountered anywhere. Other hazards include slippery coral reefs when launching at low tide, potential for strong currents in the tidal estuary, and the isolation meaning no quick rescue is possible. Notable sights include Kings Cascade, a waterfall flowing into the river, and the historically significant Mermaid Tree at nearby Careening Bay. The overall experience is one of expedition-level challenge in a spectacular, rugged, and unforgiving wilderness with significant historical exploration links. There are no facilities or amenities for paddlers; all food, water, and safety equipment must be carried in. The best season for paddling is not explicitly stated, but accounts mention expeditions during the early March wet season, which brings very high temperatures, cyclones, and deluges, suggesting this is a highly challenging and dangerous time to undertake a trip.