The Royals breezed through the tie overcoming League One opposition for the second consecutive round thanks largely to a wonderful performance from Gareth McCleary
Noel Hunt gave the Royals an early lead before Mikele Leigertwood doubled their lead before half-time with a stunning effort. The hosts continued to pick apart the Blades after the break with Hunt grabbing his second before Garath McLeary capped a great display with a goal of his own.
After seeing their fight for Premier League survival pick up in recent weeks, Brian McDermott elected to make six changes for the visit of the League One promotion contenders, with Adam Le Fondre, who scored two goals off the bench give the Royals a win at Newcastle in their last match, handed a starting role ahead of the rested Pavel Pogrebnyak.
For Sheffield United, it was a return to the Madejski Stadium for Dave Kitson, who made 143 appearances for Reading in two separate spells for the club.
Reading started like a team that had taken four wins from their last five games and within six minutes where ahead when a floating Hal Robson-Kanu cross met the head of Hunt, who rose well and steered it into the far corner.
That early shock seemed to compose the visitors however and halfway through the first half, Nick Blackman comfortably eased past Nicky Shorey at left-back before producing a drilled cross that left Chris Porter with the goal gaping. However, the Blades' forward somehow failed to make any contact from all but two yards out.
Danny Wilson's men went close to levelling through Porter again but his flicked header could only drift centimetres wide before Jamie Murphy latched on to some good link-up play from Kitson to fire in a shot that was straight down the throat of the Reading goalkeeper.
However, the League One outfit were left to pay for their profligacy when with half-time closing in, Leigertwood reacted quickly to a blocked Le Fondre shot, exchanged passes with wideman Gareth McCleary and produced a rasping drive that goalkeeper George Long got fingertips too but still had far too much power for the young goalkeeper and nestled in.
That second goal seemed to knock the stuffing out of the visitors and within 10 minutes of the start of the second half, the Premier League side found themselves four goals to the good. First, Hunt claimed his second of the afternoon when he expertly turned and finished after fine wing play from McCleary, before the former Nottingham Forest speed merchant burst into the box, eased inside a Blades defender before slotting it past the hapless goalkeeper.
From there, the tie was played at a pedestrian pace but Stephen Kelly still needed to be on his toes on the Reading goal-line to clear what would have been a consolation strike from Danny Higginbotham.