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Getting there & away
The Mekong delta is near Ho Chi Minh City, and Can Tho (Cần Thơ) is merely 4 hours' drive away, so it is easy to access by road, although there is only one main road, and as such it is rather crowded.
There are some flights between Ho Chi Minh City and Rach Gia, and also between Ho Chi Minh City and the island of Phu Quoc. Rach Gia can also be reached by boat or plane from Phu Quoc.
There used to be hydrofoil connections from Ho Chi Minh City to My Tho (Mỹ Tho) then to Can Tho (Cần Thơ) in about 4 hours, but the option does not exist any more. Alternatives are speed boat transfers, or for those who would enjoy unspoilt nature, cruises from Cai Be (Cái Bè) to Can Tho or back.
The Mekong delta is also a natural passageway from southern Vietnam to Cambodia, which can be entered overland or by river. Visas on entry to Cambodia are possible at some (but not all) entry points, however visas for Vietnam must be obtained in advance.
You can travel from Phnom Penh, Cambodia's capital, to Chau Doc on a boat-bus journey. You can also enter at the border crossing on the way from Kampot in southern Cambodia to Ha Tien. Bus connections are also now available between Phnom Penh and Can Tho.
There are many tours available that start in Saigon (Ho Chi Minh City). Some of them end in Saigon, others in Phnom Penh (also available the other way around: Phnom Penh to Saigon). You can book them in travel agencies and hotels in Vietnam and Cambodia. There are only a few tour operators available, however, it can be difficult to find out what tour operator is behind the tour you want to book, as many travel agencies pretend that it is their own tour and prices between agencies can vary significantly for the same tour. To make things a bit more complicated, tour operators often share buses and boats when they don't have enough travelers and they combine different tours (e.g. a 2 day and a 3 day Mekong Delta tour). You may have to change the buses often. Everybody seems to sell the same kind of tour, which is of pretty bad quality.
Beware of Mekong Tours. Their two day tour with crossing Cambodia-Vietnam border means that you spend only 4 hours on a boat. "we take air-con bus to the boat dock. First we take a cruising trip on Mekong river from Cambodia to Vietnam" in reality means, that you spend 3 hours in a bus to go to border, cross it on foot and the boat will be waiting on the other side. Next day you will visit fish farm and Cham minority village, all of them no further than 1 km from Chau Doc, after 1 hour you will be back to Chau Doc. In this one hour you will see both attractions and will travel between them.