Pick a gross thing (i.e. shit, sex, dicks, tits, cum, etc.) and take a shot every time that thing is the subject of a gross-out joke.
Pick a race/religion/sexual orientation (i.e. blacks, jews, gay people) and take a shot whenever that prohibited base is insulted.
An "And Then The Opposite Happens" joke happens. (Avoid "Big Ball Energy", cuz you'll die before the cold opening even finishes.)
A real-life celebrity/movie/brand/etc. is insulted, via an "Insult To Garbage" comparison gag.
Randall insults someone by calling them a name that's a pun on a celebrity or iconic figure, (i.e. calling Bullet "Arfie Lang", calling Kevin "Pablo Pic-Asshole", calling Dusty "Chef Boy-Fart-ee", etc.)
Somebody mentions Mickey Mouse. (Happens more often than you'd think. Also, avoid "Who Ate Wally's Waffles?".)
Someone does something perverted. If Joe Biden is involved, finish your drink.
A man and a woman eat at a restaurant and see something disgusting that looks like the food they're eating, causing the man to look at his food in disgust and the woman to vomit into her hands.
A message shows up on the screen, instructing the audience to look something up or not look something up, in regards to Tucker Carlson.
A main character dies only to come back to life later.