| 100% | LETBE | 5 | Don't mess with |
| 93% | MISTERINBETWEEN | 15 | Don't mess with him! |
| 93% | TEXAS | 5 | Don't mess with it! |
| 81% | IMBAD | 5 | "Don't mess with me" |
| 80% | CROCE | 5 | "You Don't Mess Around With Jim" singer |
| 79% | TEXAS | 5 | "Don't Mess With ___" (ad slogan) |
| 79% | CMONMAN | 7 | "Don't mess with me, bro!" |
| 79% | CROCE | 5 | "You Don't Mess Around With Jim" singer, 1972 |
| 77% | MIAMIADVICE | 11 | "Don't mess with the Hurricanes!," e.g.? |
| 77% | LETHIMCOOK | 10 | "Don't mess with that guy's process" |
| 73% | CROCE | 5 | Jim who sang "You Don't Mess Around with Jim" |
| 73% | GUNBELT | 7 | Place for a "Don't Mess With Texas" buckle, perhaps |
| 72% | ISR | 3 | Zohan's home country in "You Don't Mess with the Zohan" (Abbr.) |
| 67% | IGNORE | 6 | Don't deal with |
| 66% | RADIOEDITS | 10 | CeeLo Green's "Forget You" and the Black Eyed Peas' "Don't Mess With My Heart" |
| 62% | MRINBETWEEN | 11 | "Don't mess with" him, per an old song lyric ... or a hint to 18-, 20-, 55- and 58-Across |
| 61% | OPT | 3 | Don't participate, with "out" |
| 61% | GAMES | 5 | Don't play ___ with me |
| 61% | BUSINESS | 8 | Don't mix __ with pleasure |
| 61% | OPT | 3 | Don't participate, with ''out'' |
| 60% | BEG | 3 | Don't follow through, with "off" |
| 60% | ADDER | 5 | Don’t start run with snake |
| 60% | BEG | 3 | Don't follow through, with ''off'' |
| 60% | SCISSORS | 8 | Don't run with these |
| 57% | BATHWATER | 9 | Don't throw the baby out with it |
| 57% | BATHWATER | 9 | Don't throw the baby out with this |
| 57% | CLASH | 5 | Don't go together, as plaids with stripes |
| 57% | KID | 3 | Mess with |
| 56% | ELO | 3 | Don't bring this orchestra down with Strange Magic |
| 55% | DEBRA | 5 | Messing with lines |