Background: High-impact chronic pain (HICP) involves substantial interference in functioning, affects 8.5% of the population, and leads to higher health care costs relative to low-impact chronic pain (LICP). Behavioral interventions such as virtual reality (VR) offer scalable and accessible treatment, but testing is needed to ensure durable effectiveness in HICP. We conducted a secondary analysis of the largest real-world dataset for a therapeutic skill-based VR vs a sham VR control to test treatment efficacy in HICP vs LICP. Relative to LICP, we found significantly larger (and clinically meaningful; ie, ≥2 points) pain interference and pain intensity reductions for HICP at end of treatment and 1 year posttreatment. End-of-treatment reduction in pain interference reclassified 70% (114/163) of participants with HICP as LICP, and this improvement held at 1 year posttreatment (104/155, 67%). Objective: This study examined the effectiveness of a 56-session skill-based VR therapy in HICP at 2 years posttreatment and compared the effects with those on LICP. Methods: We conducted a secondary analysis of the skill-based VR sample (536/1067, 50.2%) at 2 years posttreatment from a randomized controlled trial involving an in-home chronic low back pain sample that was recruited and tested online and was diverse (female: 411/536, 77%; non-White individuals: 166/536, 31%; high school or lower educational level: 102/536, 19%; mean age 50.8 years) and had clinically severe pain at baseline (intensity=6.6; interference=6.2; 42% with severe or complete disability). Focusing on the skill-based VR participants (536/1067, 50.2%) and using a validated approach, we classified participants at baseline as either HICP (baseline Brief Pain Inventory pain interference score>7) or LICP (baseline Brief Pain Inventory pain interference scoreP<.001 in all cases at years posttreatment compared to participants with licp hicp had clinically meaningful reductions pain interference ci effect size="1.12)" and intensity posttreatment. importantly reduced scores reclassified of the as licp. no serious adverse events or side effects were reported. conclusions: patients experience severe that drives high health care use. skill-based vr therapy demonstrated durable related outcomes largest benefits observed subgroup. these results suggest a vr-delivered produces population is frequently overmedicalized undertreated behavioral interventions. findings home-based offers scalable treatment option for this underserved population.>