It was a daunting task to step up from assistant to replace Pep Guardiola in the Nou Camp hot seat, taking over from a fans' idol who won a record 14 trophies in his four years in charge.
Vilanova, who turned 44 on Monday, did not command the instant respect that the former Spain international Guardiola had accrued, but he has quickly shown he is not afraid to plough his own furrow.
At Getafe on Saturday, Vilanova rested World Player of the Year Lionel Messi and Brazil international Dani Alves for a fixture Barça have often struggled with, and at a venue where champions Real Madrid fell 2-1 last month.
The side were also shorn of Andres Iniesta, Jordi Alba and Alexis Sanchez, and during the Guardiola era often struggled with the so called 'FIFA virus' after breaks for internationals.
It had been a year since Messi was last rested for a league game and after Barca were held 2-2 at Real Sociedad, Guardiola never left him out again.
Vilanova's side, however, came through with 4-1 victory at Getafe, displaying the zip and hunger that had at times been missing towards the end of Guardiola's reign.
"The philosophy and method of working is basically pretty similar, but we have a new coach, a new form of doing things and we are very happy about him being with us," Iniesta told uefa.com.
"He knows us very well and I am confident things will go well."
Cesc Fabregas played in Messi's 'false nine' role and he helped set up the first goal for Adriano, before Messi entered the fray in the second half to bag a quick double, and another substitute David Villa notched the fourth.
Barca have a doubt over defender Alba who missed Saturday's game with a virus, and forward Alexis who is recovering from a muscle problem.
NO CRISIS
Captain Carles Puyol joined Iniesta on the injury list when he suffered a twisted knee ligament in the Getafe game, that has put him out for up to six weeks.
Vilanova's opposite number Unai Emery is having a tougher time settling in at Spartak, Russia's most popular and successful club with nine domestic titles between 1992-2001.
They have only taken one point from their last three league matches after being held to a 2-2 draw at unfancied Kuban Krasnodar on Saturday.
"Crisis? I don't think so," said the former Valencia boss Emery, who joined the Moscow club in May.
"We're working hard as a team but we are still a long way from a finished product. We're still trying to find the best way of organising our attack."
After missing Europe's premier club competition last season, Spartak qualified for the group stage by beating Turkey's Fenerbahce in last month's play-offs.
The Muscovites will be without injured captain Sergei Parshivlyuk (knee), Brazilian striker Welliton (thigh) and Argentina defender Nicolas Pareja (calf), while Dutch midfielder Demy de Zeeuw is suspended.
Probable teams:
Barcelona: 1-Victor Valdes;
