A 3-1 victory at Malaga on Sunday completed a Spanish best first half of a La Liga season with 55 of a possible 57 points in the bag, surpassing Guardiola's 52-point record for the same spell two years ago.
Holders Barca are back in action against fifth-placed Malaga at Camp Nou on Wednesday in a Copa del Rey quarter-final first leg, when cancer sufferer Vilanova has the chance to move a step closer towards his first piece of silverware.
Guardiola amassed 14 trophies from a possible 19 before he stepped aside last May, and Vilanova, having lost out to Real Madrid in the season-opening Spanish Super Cup in August, has his eyes on a May 18 Cup final.
Many in the local media have already declared Barca league champions as they hold an 11-point advantage over second-placed Atletico Madrid and an 18-point lead over ailing champions Real, but Vilanova was being prudent on Sunday.
"The league isn't won yet. I am a fan of mathematics," he said after the Malaga game.
"It will get more difficult from now on. Coming up we have the cup and the Champions League. We aren't invincible. If we ease up, we will lose games."
Vilanova was Guardiola's assistant and remains a close personal friend, but his early success has been all the more impressive considering he was forced to constantly re-jig his defence at the start of the campaign.
A string of injuries to defenders, which included losing first-choice centre backs Carles Puyol and Gerard Pique for two months apiece, tested his abilities while he appears to have solved the riddle of how to blend Cesc Fabregas into the side.
The former Arsenal captain was overlooked by Guardiola for key games towards the end of last season but has now become a fixture in Barca's slick-passing midfield alongside Xavi, Andres Iniesta and Sergio Busquets.
Guardiola had a special relationship with World Player of the Year Lionel Messi, who was too distraught to even attend his former boss's farewell news conference, but the change in coach has not disrupted the Argentine's incredible goal-scoring rhythm.
The only negative for Vilanova so far has been the need for him to have a second round of throat surgery, after having had a tumour removed from his saliva glands in November 2011.
The 44-year-old is still combining chemotherapy and radiotherapy treatment with his work after last month's second operation but is keen to play down his illness.
"I am well and able to work," he said. "But in my case, I love football. To be with the players, to kick a ball and to train, there is no better therapy.
"I want to be the protagonist for my work, not for my illness."
Malaga, who have also reached the Champions League last 16, gave a good account of themselves at the Rosaleda on Sunday despite the scoreline and remain dangerous opponents.
"I don't think this game sets a benchmark for the Cup encounters," Vilanova said. "We will probably use different players and so will they. Each duel is unique."
The victors will go on to meet either 2011 winners Real or Valencia who, with a La Liga fixture at the Mestalla next weekend included, will play each other three times in the next week and a half.
Jose Mourinho's faltering side host the last eight first leg on Tuesday after a run of only two wins from six games in all competitions, but will have leading scorer Cristiano Ronaldo back from suspension.
An improving Valencia, under new coach Ernesto Valverde, have won seven of their last eight games in all competitions.
On the other side of the draw, there is an eye-catching clash between Atletico and Real Betis at the Calderon on Thursday.
The last quarter-final sees 2010 winners Sevilla visit Real Zaragoza on Wednesday. The second legs are next week.