Introduction: Youth living with HIV (YLWH) experience higher rates of mental illness than their peers. Holistic care for YLWH may involve adopting mental health screening programs into comprehensive HIV care to help identify and address mental health concerns in young people. We explored various contexts, procedures, and safety measures throughout the integration and maintenance of a mental health screening program for adolescents attending an HIV referral clinic in Gaborone, Botswana. Methods: Implementation goals included a safety goal of 100% appropriate referral rate for emergency cases, and a screening goal of 70% of the approximately 1100 adolescent and young adults who were clients of the clinic at least once in the one year review period. Frequent meetings with the behavioral health team and relevant clinic staff were conducted to determine when, where and how to screen the clients. Referral procedures and an emergency protocol for certain “red flag” behaviors was developed to facilitate a warm handing off to trained mental health professionals along with a backup for non-mental health clinicians to assist in the absence of the PSS team. Every other week severe score case reports were produced by the screening team to prevent loss to follow up of suicidal ideation, hallucination or very high scores. Mild to moderate cases were referred to clinicians trained in brief intervention therapy. Results: Of the 846 clients screened, 191 (19.2%) had severe scores. Eight (4.1%) of these 191 severe case scores were either not immediately reported, or were inappropriately referred. Two of those eight had suicidal ideation and were not immediately referred but were appropriately followed up after being identified during bimonthly implementation team meetings. Identifying a specific trained person tasked with facilitating the screening was found to be most helpful. As was training the clinicians in methods to respond to mild to moderate results, particularly during unavailability of PSS team members. A clear and detailed protocol for severe cases was also noted as a key element in keeping the screening program safe. Conclusions: Establishing a universal screening program in an LMIC is possible with the consideration of various contextual factors.