The tension placed on the 12 string Guitar by the strings is high, Some performers prefer the richness of an open tuning due to its near-orchestral sound. For a very complex plucked-string sound, the 12-string can be set to standard tuning (or possibly an octave lower), then the top one and low two string pairs can be tuned to whole-tone intervals. The usual gamut of guitar tunings are also available. Many performers who play the twelve-string guitar use an ordinary six-string guitar as their primary instrument, switching to the twelve-string guitar for certain songs that seem to call for a brighter sound.

The greater number of strings complicates playing, particularly for plucking or picking. The gap between the dual-strings is usually narrower than that between the single-string of a conventional six-string guitar, so more precision is required with pick or fingertip when not simply strumming chords. Nevertheless, with practice, the twelve-string guitar is not unduly difficult to play. It is, however, generally used in a fairly restricted role that emphasizes its strengths: rich ringing, full-bodied chords, and fast, rippling single plucked notes on the twinned strings. Twelve-string guitars are available in both acoustic and electric form. However, it is the acoustic type that is popular.