Background: Multiple Sclerosis can affect the patients’ and their families’ life. In this regard, the collaborative care model could be useful. This study aimed to investigate the effect of the collaborative care model on hope in patients with Multiple Sclerosis (MS) and their family caregivers.Methods: This randomized controlled clinical trial was conducted in May to September 2015 on 60 patients with MS referring to the MS Society of Khuzestan province and 60 family caregivers. After block randomization, the intervention groups (patients and caregivers) received 8 intervention sessions based on collaborative care model over 12 weeks. The data were collected using Snyder’s adult hope scale and a demographic questionnaire at baseline and 12 weeks after the beginning of the intervention. Data analysis was conducted through SPSS, version 19, using frequency, mean, Chi-square, independent, paired t-tests and Fisher’s exact test (P˂0.05). Results: The results of independent t-test before the intervention showed no significant differences between the patients in the intervention (42.76±8.75) and control groups (43.13±7.20) (P=0.86) and caregivers in the intervention (50.26±5.79) and control groups (49.23±6.71) (P=0.52), regarding the score of hope. However, a significant difference was found in this regard 12 weeks after the beginning of the intervention, between the patients in the control (43.63±6.97) and intervention groups (47.96±8.72) (P=0.03), and caregivers in the control (50.66±5.79) and intervention groups (53.80±4.71) (P=0.02)Conclusion: The collaborative care model promoted hope in patients with MS and their family caregivers. Hence, this model can be used by healthcare personnel for promoting hope among patients and caregivers.Trial Registration Number: IRCT2015051121474N2