Design Week takes over Milan for one week each April, and that week decides what you pay for a room. If design is why you are going, it is the only week that matters. If it is not, avoid it, and you get a calm, mild city, with highs around 19°C, at ordinary prices. The week moves, falling early in the month in some years and late in others, so get the dates of the Salone del Mobile, the fair at its centre, before you look at flights.
For Design Week, reserve a room months ahead, the day your dates are fixed, and only then think about flights. When the centre is full, stay near a stop on the red M1 line, which runs straight out to the fair.
The Salone itself is a trade fair at Rho Fiera Milano, on the north-west edge of the city, about half an hour from the centre on the M1 to Rho Fieramilano. Most of the week is for trade visitors. As a rule the public gets the final weekend, and tickets are sold only through the official Salone site.
The Fuorisalone is the other half of Design Week, and most of it is free: hundreds of shows in showrooms, courtyards and former factories, grouped into districts. Brera Design District is central and polished. Tortona, a former industrial area, is more experimental, Isola younger and scrappier, and 5Vie leans towards craft. Do two districts a day on foot. Crossing the city between openings eats an afternoon.
On 25 April, Liberation Day, the city holds its main march. It normally sets off from Porta Venezia in the afternoon and ends with speeches in Piazza del Duomo, and roads along the route close. In a year when the Salone's public weekend lands on the 25th, as it can, leave the cathedral for another day and allow extra time to cross the centre.
Whatever week you choose, the Last Supper is the booking most likely to go wrong. Tickets for Leonardo's mural at Santa Maria delle Grazie are released in blocks of several months at a time, and the good slots go fast, so find out when your block opens and be online that day. If you miss it, try again on a Wednesday, when a small batch for the following week is released online for individual visitors.