Response surface methodology was used to assess the effects of osmotic solution concentration (40–60°Brix), process temperature (20–40 °C) and vacuum pulse application time (0–20 min) at 100 mbar on water loss (WL), weight reduction (WR), solid gain (SG), water activity (aw), colour parameters and mechanical properties of guava slices. Optimal process conditions were determined through the desirability function approach and quality characteristics of osmotically dehydrated guavas were analysed. Only models obtained for WL, WR and aw were suitable to describe the experimental data. The desirability function showed that optimal conditions for osmotic dehydration of guavas were: osmotic solution concentration at 60°Brix, process temperature at 32 °C and 20 min of vacuum pulse application. Under optimal conditions, colour and mechanical properties of treated guavas were similar to fresh fruit, presenting WL of 29.01 g/100 g, WR of 25.91 g/100 g, SG of 3.10 g/100 g and aw of 0.979.