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Abstract Background Niger is a large country with many distant locations that can be difficult to access because the Sahara Desert covers 80% of the country’s land. In Niger, just 49% of residents have access to a health centre within 5 km of their house. Health care may be difficult to access in the Diffa region of Niger, as non-state armed groups strike on a regular basis and floods cause a high rate of vulnerability. This study looked at how mobile clinics can improve healthcare accessibility for vulnerable populations in the Diffa region. Methods This was a descriptive-comparative study conducted over the period from 15 August 2022 to 15 October 2022, using three months’ mobile outreach clinic to improve health outcomes in five districts of the Diffa region, including Bosso, Diffa, Goudoumaria, Mainé Soroa, and N’guigmi. Results During the three months of mobile outreach clinic, 42,251 people were sensitized about mobile outreaches and 12,004 were treated. A total of 18,708 vaccine doses were delivered to children aged 0–11 months, with Maine Soroa, Goudoumaria, Bosso, Diffa, and N’guigmi districts accounting for 29.24%, 24.62%, 18.54%, 18.05%, and 9.5%, respectively. In the same line, Goudoumaria, Bosso, and Maine Soroa districts recorded relatively high antenatal clinic (ANC) attendance percentages of 27.85%, 25.62%, and 21.89%, respectively. Furthermore, mobile clinic outreach provided a variety of healthcare treatments, both curative and preventative. Mobile Clinic 2 increased vaccine dose received among children aged 0–11 months by 1.11% (95%CI: 0.15%-2.06%, P = 0.023) when compared to Mobile Clinic 1. In the same line, mobile clinic showed a statistically significant increase of ANC between the three clinical rotations (P = 0001), showing an increased ANC update over time. Conclusion This study found that mobile outreach clinic can play an important role in improving healthcare access for vulnerable populations in the Diffa region. However, well-designed, and frequent mobile clinic outreach should be planned and included in the country’s public health policy.