I. Amp without effects loop

If your amp doesn't have an effects loop, you only have one option, as demonstrated below. You should set your output mode to "Combo Front" or "Stack Front" (see output modes section). These modes allow you to tweak the tone before it hits your amp to compensate for how your amp's pre-amp will color the tone. Set the amp/line switch to amp. Note that the "[]" section represents an optional section.

This setup is undesirable because you cannot bypass your amp's pre-amp. Whatever coloration it has on the tone cannot be avoided, only compensated for using the Pod's limited controls as mentioned above. Also, you have to run all your effects before said pre-amp, which may prevent you from achieving the dynamics you desired.

The only benefit is that if you like your amp's pre-amp, you can use it instead of the amp modeling on the Pod, using the Pod only for before pre-amp effects. But then why do you have a Pod anyway? I always try to get the most out of whatever gear I already have before even contemplating a new purchase; but honestly, unless you have a REALLY, REAAAAALLY transparent amp, I think you should start looking for a new amp, even if it’s a $300 to $400 1x12 combo.

The Pod works best when run into the effect's loop return of an amp. This bypasses the pre-amp and sends the tone directly into the power amp section of the amp. I use a used 1x12 Spider Valve Mk I combo, which I bought for less than the price of a Pod HD 500. For my purposes it works great. If I need more volume from it, I’ll get a 1x12 or 2x12 extension cab.

Guitar > [external effects >] Pod guitar in

[Pod effects loop out > external effects > Pod effects loop return]

Pod unbalanced out > [external effects >] Amp guitar in

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II. Pod as Effects Only after pre-amp

Here you will have the amp/cab model block in the Pod disabled (turned off or set to "no amp"). It doesn't matter what output mode you use, but to be safe (in case you one day decide to use the amp models and forget about this setup) choose one consistent with how you're hooking it up - Stack or Combo Power Amp.

Note: if your amp's level on the effects loop send is too hot for the Pod, and you cannot turn the send level down on the amp, you may have to run the amp's effects send to the Pod's effects loop return, then turn down the level on the effects loop return on the Pod.

Guitar > Amp guitar in

Amp effects loop out > Pod guitar in OR Pod effects loop return

Pod unbalanced out > Amp effects loop return (power amp in)

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III. Simple setup for amp with effects loop

This hookup is nearly the same as above, but you run into the effects loop return (power amp in) on the amp. Use "Combo Power Amp" or "Stack Power Amp" output mode (or "Studio/Direct" and make sure you choose "no cab"), and set the line/amp switch to line.

Here you bypass your amp's pre-amp completely, and you use the Pod's amp modeling instead. This gives you a very clean tone - power amps usually don't color the tone very much, at least not until you start really pushing the amp. In that case, you should see the "pre" vs. "full" section for help in choosing the right amp models for your power amp.

The downside is that you do not have the option to use your amp's pre-amp. If you want that option, you have to use the 4 cable method, described below.

Guitar > [external effects >] Pod guitar in

[Pod effects loop out > external effects > Pod effects loop return]

Pod unbalanced out > [external effects >] Amp effects loop return (power amp in)

This is how I run the Pod to my Spider Valve combo.

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