Mixed mode assembly is built against version ‘v2.0.50727′ of the runtime

Try to use this exact startup tag in your app.config under configuration node

<startup useLegacyV2RuntimeActivationPolicy="true">
    <supportedRuntime version="v4.0" sku=".NETFramework,Version=v4.0"/>
    <requiredRuntime version="v4.0.20506" />
  </startup>

The exception clearly identifies some .NET 2.0.50727 component was included in .NET 4.0. In App.config file use this:

<startup useLegacyV2RuntimeActivationPolicy="true" /> 

It solved my problem

Please add attribute useLegacyV2RuntimeActivationPolicy="true" in your applications app.config file.

Old Value

  <startup>
    <supportedRuntime version="v4.0" sku=".NETFramework,Version=v4.5.1"/>
  </startup>

New Value

  <startup useLegacyV2RuntimeActivationPolicy="true">
    <supportedRuntime version="v4.0" sku=".NETFramework,Version=v4.5.1"/>
  </startup>

It will solve your problem.

I actually had this identical issue with the inverse solution. I had upgraded a .NET project to .NET 4.0 and then reverted back to .NET 3.5. The app.config in my project continued to have the following which was causing the above error in question:

<startup>
  <supportedRuntime version="v4.0" sku=".NETFramework,Version=v4.0"/>
</startup>

The solution to solve the error for this was to revert it back to the proper 2.0 reference as follows:

<startup>
  <supportedRuntime version="v2.0.50727"/>
</startup>

So if a downgrade is producing the above error, you might need to back up the .NET Framework supported version.

If the error happens with error column "File" as SGEN, then the fix needs to be in a file sgen.exe.config, next to sgen.exe. For example, for VS 2015, create C:\Program Files (x86)\Microsoft SDKs\Windows\v10.0A\bin\NETFX 4.6 Tools\sgen.exe.config. Minimum file contents: <configuration><startup useLegacyV2RuntimeActivationPolicy="true"/></configuration>

Source: SGEN Mixed mode assembly

Enabling the legacy from app.config didn't work for me. For unknown reasons, my application wasn't activating V2 runtime policy. I found a work around here.

Enabling the legacy from app.config is a recommended approach but in some cases it doesn't work as expected. Use the following code with in your main application to force Legacy V2 policy:

public static class RuntimePolicyHelper
{
public static bool LegacyV2RuntimeEnabledSuccessfully { get; private set; }

static RuntimePolicyHelper()
{
    ICLRRuntimeInfo clrRuntimeInfo =
        (ICLRRuntimeInfo)RuntimeEnvironment.GetRuntimeInterfaceAsObject(
            Guid.Empty, 
            typeof(ICLRRuntimeInfo).GUID);
    try
    {
        clrRuntimeInfo.BindAsLegacyV2Runtime();
        LegacyV2RuntimeEnabledSuccessfully = true;
    }
    catch (COMException)
    {
        // This occurs with an HRESULT meaning 
        // "A different runtime was already bound to the legacy CLR version 2 activation policy."
        LegacyV2RuntimeEnabledSuccessfully = false;
    }
}

[ComImport]
[InterfaceType(ComInterfaceType.InterfaceIsIUnknown)]
[Guid("BD39D1D2-BA2F-486A-89B0-B4B0CB466891")]
private interface ICLRRuntimeInfo
{
    void xGetVersionString();
    void xGetRuntimeDirectory();
    void xIsLoaded();
    void xIsLoadable();
    void xLoadErrorString();
    void xLoadLibrary();
    void xGetProcAddress();
    void xGetInterface();
    void xSetDefaultStartupFlags();
    void xGetDefaultStartupFlags();

    [MethodImpl(MethodImplOptions.InternalCall, MethodCodeType = MethodCodeType.Runtime)]
    void BindAsLegacyV2Runtime();
}
}

For me this was thrown when running unit tests under MSTest (VS2015). Had to add

<startup useLegacyV2RuntimeActivationPolicy="true">
</startup>

in

C:\Program Files (x86)\Microsoft Visual Studio 14.0\Common7\IDE\CommonExtensions\Microsoft\TestWindow\TE.ProcessHost.Managed.exe.config

Mixed-Mode Assembly MSTest Failing in VS2015

Try to use another config file (not the one from your project) and RESTART Visual Studio:

C:\Program Files (x86)\Microsoft Visual Studio 11.0\Common7\IDE\CommonExtensions\Microsoft\TestWindow\vstest.executionengine.x86.exe.config
(32-bit)

or

C:\Program Files (x86)\Microsoft Visual Studio 11.0\Common7\IDE\CommonExtensions\Microsoft\TestWindow\vstest.executionengine.exe.config
(64-bit)