Will be in town from June 2 - June 7 to play Colossus and cash. How much will I hate life if I stay downtown?

Depends. Where downtown, do you have a car, and how much do you hate life in general?

I stayed downtown the last two years during the Colossus (which I played in, briefly). Wasn't a big deal. I was able to get up and out to the Rio in plenty of time for the morning flights (once via cab, once driving myself) Now I would Uber/Lyft, prolly, but I'm a late adopter (trailing edge is where it's at!) Also, the Nugget and Binion's have pretty decent series going on if you'd rather play downtown once you bust out. I did, and scored a nice win last year.

I can see the draw of having a room at the Rio, but I also see a big upside to getting the F outta there after a long day/night of grinding.

FWIW, I'm doing a VRBO apartment off strip and away from downtown this year. What I save on room costs will more then cover the Lyft bill, and I don't have to eat out every meal.

I think that staying downtown is the right move for many grinders, double if you're on your own. In many places the rooms aren't bad, there are cheaper food alternatives, and there are tournaments and games at some of the downtown casinos (as Az pointed out). Why waste money on overpriced rooms and food on the strip?

Years ago I would stay at the cheapest rooms I could find, preferably walking distance from Binion's (where the WSOP was held years ago). Some of them were pretty bad, but all I used them for was showering and sleeping, so I really didn't care (plus I was there for 10 days or more, so the savings added up). I rented a car so I could drive to the strip casinos and around town for whatever (The Mirage had the main poker room back then).

You could easily save over $100 per night if you stay downtown, and that's $500 for the trip. Maybe spend $100 or so on uber or cabs to get to the Rio or strip (there's a free shuttle from Ballys to the Rio when you're on the strip). Is that $400 better spent on a buy-in or two in a 1/2 game, or a few tournaments? That's for you to answer. But for many grinders the answer is yes.

Good luck with your decision and at the games.

If you're fine with playing 1/2, the Golden Nugget seemed like a good place to play, if you like playing against bad regs. (There are some poker vloggers who have sessions at the GN.) Apparently, the $2/hour in comps you get there can be used at any Landry's restaurant in the country. (Includes Morton's, McCormick & Schmick's, Claim Jumper, Rainforest Cafe, and a bunch of stuff I haven't heard of.) I'm not sure if they get 2/5 when their tournament series is running. You can get reasonable meals under $10 downtown.

You have the option of spending part of your stay downtown. If you think you will be making return trips to Vegas, it's probably worth spending a couple of nights downtown for future reference.

I assume the downtown hookers are both cheaper and less attractive.

Good advice itt

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Did OP say ha has a vehicle?
Zero issues with wheels... without, you could run into costs you might not like.

One thing I forgot to mention. Downtown is very noisy now. When I stayed there years ago Fremont Street was open to traffic and there was very little going on outside besides the normal stuff. Now, with the Fremont Street Experience there are bands playing on every street, bars outside serving all manner of drunks, and a lot of other noisy stuff going on (and lots of flashing lights). Make sure you get a room facing away from that area if you want to sleep late (or early), especially if on a low floor at one of the Fremont Street hotels.

There are probably a lot more pick-pockets and muggers too. So be alert.

No car, would uber or lyft. It's between $200 all in staying at the D or similar or $500-600 for PH (5 nights). The off strip meal prices are attractive. Aside from Colossus most play would be Bellagio, possibly PLO at Aria. If I stay downtown would be open to playing at the nugget some.

You'll be fine. For a short stay the strip might be good too. Also, the bus is very doable here. Especially for a short stay.

The 4 Queens downtown has a decent rating on Yelp and is ~ $50 per night. The Golden Nugget a block away has their own tournament series going on if you want to catch an event there.

Downtown is OK I guess. Mainstreet Station and California both have rooms facing away from the noise and are comfortable.

You may want to consider other off strip properties such as Orleans or Gold Coast. Much closer to the Rio, prices can be lower. Last year the poker room action at Orleans was pretty hot.

Don't assume you can get a table for a cash game during the Colossus. Wait lists where 100+ deep the last two years.

Not to mention, less poker tables available this year with Venetian gutting their room.