Diagnosis of chronic disease in a child can result in unresolved grief (UG) in parents. This study aimed to evaluate the efficacy of psychological insight-oriented therapy (IOT) as a treatment for UG compared to disease related education in parents of children with cystic fibrosis (CF). Sequence of delivery, first IOT then disease related education (or vice versa ) was also examined, to let all participants experience both interventions. Parents were screened for UG. Parents with UG were randomised to either five one-hour sessions of IOT or five one-hour sessions of education. Measures were assessed pre-intervention, after the first intervention period (primary efficacy assessment), and after the second intervention period (swapping intervention). Forty-seven parents were screened of which 46.8% (22/47) had UG. Median duration of UG was 5 years (range: 6 months to 14 years). Anxiety (50% vs. 20%, p =0.03) and stress (59% vs. 28%, p =0.03) were significantly more prevalent in parents with UG. There was no difference between arms in the odds of UG resolving either following the first intervention period (OR 0.88; 95%CI 0.5, 1.5) or the second intervention period (OR 0.91; 95%CI 0.5, 1.6). While not statistically significant, adjusted mean values of all nine mental health measures were lower in the IOT (first) arm compared to the ED (first) arm, following the first intervention period. Conclusions: UG is a significant burden for families affected by CF. Provision of disease related education and psychological support, regardless of sequence, can result in resolution of grief.