To compare the in vivo surface wettability of silicone hydrogel (SiHy) contact lenses pre-soaked overnight in different multipurpose solutions (MPS) and normal saline. In this double-blinded, randomized and self-controlled study, 36 subjects were fitted with three pairs of contact lenses (senofilcon A) pre-soaked overnight in five different MPS and saline in a randomized order. Each pair of lenses (pre-soaked in two different solutions the night before) were worn for 15min before assessment of pre-lens non-invasive tear break-up time (PL-NITBUT) using the Medmont corneal topographer (video recording). Corneal integrity was assessed using a slit lamp and a resting interval of 20min was allowed between each pair of lenses to ensure post-lens wear corneal integrity. Thirty subjects completed the study. The median PL-NITBUT ranged from 2.84s to 3.08s with lenses pre-soaked in different MPS, compared to 2.78s with lenses pre-soaked in saline. No significant differences in PL-NITBUT were found among lenses pre-soaked in different solutions (p=0.647). In vivo surface wettability, in terms of PL-NITBUT after 15min of lens wear, of senofilcon A contact lenses pre-soaked overnight in different MPS were not significantly different from those pre-soaked in saline.