Background: Adults 50 and older make up approximately 50% of persons living with HIV. Multiple co-morbidities are common among this group, including chronic pain and substance abuse, yet little is known about the daily factors that either enhance or inhibit these experiences or behaviors. This study explored daily drivers of substance use, pain, and relief from pain among older adults living with HIV utilizing ecological momentary assessment (EMA). Method: Participants (N=55), ages 49–71, completed seven consecutive days of daily EMA online surveys prior to treatment initiation within a randomized controlled trial. Multilevel modeling tested predictors of pain, substance use, and relief from pain by examining within- and between-person relationships. Results: Results revealed an associational, reciprocal relationship between daily worst pain and daily drinking, where greater worst pain ratings predicted heavier drinking and heavier drinking predicted greater daily and overall pain. Greater happiness and poorer quality of sleep predicted greater daily worst pain. Exercising and overall confidence to cope with pain without medication were associated with lower levels of daily worst pain. Finally, spending less time with a loved one over time and reporting any coping behavior were associated with relief from pain. Conclusion: Investigation of daily factors that drive pain and substance use behaviors among this unique population help inform which daily factors are most risky to their health and well-being. Alcohol use emerged as the only substance associated with both driving pain and responding to pain. Findings suggest key points for prevention and intervention.