Reflecting on the album in a 2008 interview, singer/bassist Dan Andriano considered it a turning point for the band musically:
I would have to say From Here to Infirmary definitely started to shape things up with more of a straight up rock kind of sound. I think the previous two albums [(1998's Goddamnit and 2000's Maybe I'll Catch Fire)] are really great, but are a bit meandering. I think [From Here to Infirmary] is when Matt [Skiba] and I both realized that we wanted to tighten the screws a bit, simplify things a little and focus more on punching you in the nuts with our rock; Metaphorically speaking of course.
Critical reaction to the album was mixed. Ari Wiznitzer of Allmusic called it a slump for the band and "a definite low point in Alkaline Trio's catalog," criticizing its "lighter, more mainstream sound," which "really doesn't complement Matt Skiba and Dan Andriano's foul-mouthed poetry as well as their earlier abrasive sound. Adding to the disappointment is that this is the first Alkaline Trio release to have any filler, as many of the songs seem painfully tossed off (and probably were, as the band has been so prolific)." Matt Hendrickson of Rolling Stone was more praising of the album's qualities, remarking that the band "deliver[s] catchy punk pop with sharp elbows and a wry sense of humor" and that "What saves them from the gutter are some effortless hooks and Skiba's hysterical lyrics."
John Dark of Pitchfork Media remarked "There's quite a bit that Alkaline Trio's music is not. It's not challenging, ambitious, or visionary. It's not clever or self-aware. It's not even terribly skillful. But what it is, is tasty. Pure musical junk food: fast, greasy, and crafted for a general palate." He criticized some of the music as "a tad too derivative for your average rock snob", but praised the band's lyricism and ability to turn a phrase, though noting that they would occasionally "jar you back to reality with bonehead moves like spelling out the very, very thinly-disguised metaphor in one song [("Mr. Chainsaw")] for the listener." Ultimately, though, he concluded that "for all its flaws, From Here to Infirmary remains nothing more than simply what it is: tuneful, consumable, and guiltily satisfying."