129 problems have been reported for the 2006 Mercedes Benz R350. The following chart shows the 18 most common problems for 2006 Mercedes Benz R350. The number one most common problem is related to the vehicle's engine and engine cooling with 32 problems. The second most common problem is related to the vehicle's suspension (26 problems).
The following chart shows the number of problems reported during each of the service years since the debut of the 2006 Mercedes Benz R350 in 2006.
| Service Year | Number of Problems |
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| 2022 | |
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| 2006 |
When making the decision between buying a new or used Mercedes Benz R350, the following table can be used to compare the 2006 Mercedes Benz R350 with the Mercedes Benz R350 from other model years. Note that the number of problems reported for the 2006 R350 is 129 while the average number of problems reported for the 7 model years of the Mercedes Benz R350 is 40.