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Best way to get from Frankfurt to Lake Constance

While planning our vacation the end of April we are trying to find the best way to get from Frankfurt to Lake Constance. We have friends who stayed in Lindau and LOVED it. We would love to visit Mainau because we have heard that it is incredible. I believe that Lake Constance is the largest lake in Germany so as I look at a map I'm wondering if we would be better off staying in Konstanz. Thinking train from Frankfurt to either Wurzburg or Heidelberg for the first night. If we go toward Heidelberg it seems like that would enable us to stay a night or two somewhere in the Black Forest area on our way to Lake Constance. I would prefer to take trains but it seems like we would be better of with a car. If we take trains it would appear that Frankfurt to Wurzburg would be our best bet and stop in Munich on our way to Lake Constance. We can spend 4-5 nights on this portion of the trip. I would prefer to only stay in 2 hotels for this portion of the trip but my guess is we will need 3 because we don't want to travel too far the first day after our flight from the States which is why we were thinking Wurzburg or Heidelberg that first night.

We will leave Lake Constance and work our way to Vienna.

We have never been to Germany so I am completely lost here but excited! Thanks for your help.

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Lindau has a station, as have all the main towns on Lake Constance (German: Bodensee). There is a railway line running all the way around the lake.
Lindau is the better place to stay at, Konstanz is nice, but more of a big town, while Lindau is a small town on an island (bridges to the mainland), with views of the Alps on a clear day (click here).
But, you must not miss Insel Mainau (click here), which is a short bus ride north of Konstanz. As well as the railway, there are ferries criss-crossing the lake in summer (click here for website, click here for timetable).

Going via Wurzburg and Munich is a large detour - not recommended.

Recommendations: Yes, spend the first night in Heidelberg.
From there, cut through the Black Forest to Bodensee. There is a scenic rail line that cuts through the middle from Offenburg to Singen. You could do this by rail: Heidelberg - Offenburg - Singen - Lindau (according to that takes 5-6 hours and costs between €23 and €31 per person), or hire a car for 1-2 days to do the same trip. Your choice.
From Lindau, you can take a day trip to Insel Mainau and Konstanz. Some boats stop at the island, to maximise time you could do boat one way and train back.

Finally, you can take a train Lindau - Bregenz - Feldkirch and change to the main line to Vienna, which is scenic as it goes longitudinally through the Alps.