Dr. Bleed's second surgery. All of the various hard-as-hell surgeries in the game (which were usually made hard by Guide Dang It! moments) tend to become much easier once you know the trick behind them. This one, on the other hand, is a four-part Marathon Level against poison, fire, buried chunks of crystal, and finally a tapeworm that takes more hits from the battery to kill than the last tapeworm (and can quickly cause Bleed to... well, bleed out if you're not multi-tasking between cauterizing the cuts it makes and zapping it). And you have just enough time to do it all quickly and flawlessly.
Amateur Surgeon 2:
Scarlet Throbbing. The crabs move extremely quickly, deliberately avoid your cursor, and can even wrap around the screen. Once you saw off the carapace, it becomes stuck in the body, causing an open wound. The crabs also leave tiny cuts in their wake that can easily blend into the background. You then have to saw the crab again to actually kill it, and then you have to vacuum up the blood, remove the crab shell from the wound, and sew all the wounds caused by the crab shut. And there's not just one crab. There's three, and the second incision contains two at once. Worse, Scarlet is seen barely halfway through Act 1, so you won't have time to upgrade much of your equipment.
The Mystery Boss is a complete pain in the ass. Poison builds up quickly, and it's incredibly difficult to syringe out all the poison before it multiplies in another area. This is already hard enough, but add on the fact that every use of the syringe makes a small cut, the bee flies around and lands for just a second, and the fact that the time window to complete the surgery is incredibly small... be prepared to replay the surgery over and over until you complete it.
It's even worse in the mobile versions, since the flashlight (which is always where your mouse cursor is on PC) is controlled via tilting the phone. As if the surgery wasn't difficult enough...
Napoleon Trotterski. His surgery starts off easy enough, but suddenly ends with you having to spell out words on a "Speak 'N Spell". If you aren't fast enough, the Speak 'N Spell suddenly explodes, leaving flames and burn marks that'll almost certainly obscure the screen and the keys; and if you try to put out the fire/heal the burn marks directly when they're on the keyboard, the game will assume you're hitting the keyboard instead and explode a second time. Then again, it's not like you'll have any time to put out the fire, since the words start coming faster and faster, meaning that you have to spell them out while unable to see what you're supposed to be spelling because the goddamn fire is in the way. While you can use the keyboard to spell the words, the game never tells you that you can even do that, so good luck figuring that out.
It speaks to the difficulty of this surgery that Amateur Surgeon 4, which otherwise has every level from the previous games (sans Christmas Edition and the bonus levels from Amateur Surgeon 3), omitted it from the collection.
Jimmy the Spider's intestines are full of weird glowing bugs that need to be hit with the car battery. So far, anything you've needed to use the car battery on has been slow-moving, stationary, or have long rest periods. These bugs are very fast, causing frequent misses. As the bugs periodically start fires, missing with the car battery and then reviving the patient will likely cause him to die immediately due to all the fires. There are also bug eggs that spawn: these have to be moved incredibly slowly, even with maxed-out tongs, lest they explode, spawning another bug and starting a fire. Even if you don't move the eggs, they will hatch anyway if you're too slow in picking them out.
Amateur Surgeon 4:
The Partner Special for Level 54 (Dwayne Pipe), to where even using the required I.C. Wiener doesn't help that much. Worms are fast and small enemies which makes it very easy to miss them and you have to shock them three times. Also, your heart rate decreases rapidly, so you can't just shock a few of them at a time. Instead, you have to be really quick and shock as many of them as you can in one consecutive try, and if you miss a shot... well, just hope your heart rate isn't close to zero.
Level 42 (Karl Puccino from AS1) was already hard in its original version, but this revamp amplifies it for how little time you have to complete it. You have to find eight coffee bags hidden, scratch out the pus, vacuum up all the blood and pus, and stitch up the wounds in the span of one minute and thirty seconds. Not helping is the fact that having too much pus onscreen will rapidly decrease your heart rate, so it's recommended to vacuum up one or two piles of it at a time. If you want a shot at beating this level, you better have some memory of where the coffee bags are and be fast.
Level 84 (Junkyard Guts' second surgery from AS1) is extremely hard if you play on Sudden Death mode or try to go for a no-hit run. One of the tasks is pulling out five needles in a row from the time bomb, which all are very narrow and require a lot of precision and accuracy to successfully pull out without harming Guts.
Level 92 (Useful Brother) and its Partner Special are both extremely difficult. If the ice ants aren't hard enough to deal with, then the confusing cluster of maladies Max Chaos causes in the Partner Special will make it harder.
