Roussimoff returned in the winter of 1990, but it was not to the World Wrestling Federation. Instead, Roussimoff made an interview appearance for Herb Abrams' fledgling Universal Wrestling Federation on October 11 in Reseda, California. (the segment aired in 1991). He appeared in an interview segment with Captain Lou Albano and put over the UWF. The following month on November 30 at a house show in Miami, Florida, the World Wrestling Federation announced his return as a participant in the 1991 Royal Rumble (to be held in Miami, FL two months later). Roussimoff was also mentioned as a participant on television but would ultimately back out due to a leg injury.
His on-air return finally took place at the WWF's Super-Stars & Stripes Forever USA Network special on March 17, 1991, when he came out to shake the hand of The Big Boss Man after an altercation with Mr. Perfect. The following week at WrestleMania VII, he came to the aid of the Boss Man in his match against Mr. Perfect. Roussimoff finally returned to action on April 26, 1991, in a six-man tag-team matchup when he teamed with the Rockers in a winning effort against Mr. Fuji and the Orient Express at a house show in Belfast, Northern Ireland. On May 10 he participated in a 17-man battle-royal at a house show in Detroit, which was won by Kerry Von Erich. This was Andre's final WWF match, although he was involved in several subsequent storylines. His last major WWF storyline following WrestleMania VII had the major heel managers (Bobby Heenan, Sensational Sherri, Slick, and Mr. Fuji) trying to recruit Roussimoff one-by-one, only to be turned down in various humiliating ways (e.g. Heenan had his hand crushed, Sherri received a spanking, Slick got locked in the trunk of the car he was offering to Roussimoff and Mr. Fuji got a pie in his face). Finally, Jimmy Hart appeared live on WWF Superstars to announce that he had successfully signed Roussimoff to tag-team with Earthquake. However, when asked to confirm this by Gene Okerlund, Roussimoff denied the claims. This led to Earthquake's attacking Roussimoff from behind (injuring his knee). Jimmy Hart would later get revenge for the humiliation by secretly signing Tugboat and forming the Natural Disasters. This led to Roussimoff's final major WWF appearance at SummerSlam '91, where he seconded the Bushwhackers in their match against the Disasters. Roussimoff was on crutches at ringside, and after the Disasters won the match, they set out to attack him, but the Legion of Doom made their way to ringside and got in between them and the Giant, who was preparing to defend himself with one of his crutches. The Disasters left the ringside area as they were outnumbered by the Legion of Doom, the Bushwhackers and Roussimoff, who struck both Earthquake and Typhoon (the former Tugboat) with the crutch as they left. His final WWF appearance came at a house show in Paris, France, on October 9. He was in Davey Boy Smith's corner as the Bulldog faced Earthquake. Davey Boy hit Earthquake with Roussimoff's crutch, allowing Smith to win.
After WrestleMania VI, Roussimoff spent the rest of his in-ring career in All Japan Pro Wrestling (AJPW) and Mexico's Universal Wrestling Association (UWA), where he performed under the name "André el Gigante." He toured with AJPW three times per year, from 1990 to 1992, usually teaming with Giant Baba in tag-team matches. He also made a couple of guest appearances for Herb Abrams' Universal Wrestling Federation, in 1991, feuding with Big John Studd, though he never had a match in the promotion. He did his final tour of Mexico in 1992 in a selection of six-man tag matches alongside Bam Bam Bigelow and a variety of Lucha Libre stars facing among others Bad News Allen and future WWF Champions Mick Foley & Yokozuna. Roussimoff wrestled his final match for AJPW in 1992, after which he retired from professional wrestling.