Objective: Obsessive-compulsive disorder (OCD) with poor insight has severe consequences for patients; nonetheless, no randomized controlled trial has ever been performed to evaluate the effectiveness of any treatment specifically for poor-insight OCD. A new psychotherapy for OCD, the inference-based approach (IBA), targets insight in OCD by strengthening normal sensory-driven reality testing. The goal of the present study is to compare the effectiveness of this new treatment to the effectiveness of cognitive behavior therapy (CBT) for patients with OCD with poor insight. Method: A randomized controlled trial was conducted, in which 90 patients with OCD with poor insight received either 24 CBT sessions or 24 IBA sessions. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcome measures were level of insight, anxiety and depressive symptoms, and quality of life. Mixed-effects models were used to determine the treatment effect. Results: In both conditions, a significant OCD symptom reduction was reached, but no condition effects were established. Post hoc, in a small subgroup of patients with the worst insight (n = 23), it was found that the patients treated with the IBA reached a significantly higher OCD symptom reduction than the patients treated with CBT [estimated marginal mean = -7.77, t(219.45) = -2.4, p = 0.017]. Conclusion: Patients with OCD with poor insight improve significantly after psychological treatment. The results of this study suggest that both CBT and the IBA are effective treatments for OCD with poor insight. The IBA might be more promising than CBT for patients with more extreme poor insight.