Purpose To report change in strabismus-specific health-related quality of life (HRQOL) following treatment with prism. Design Retrospective cross-sectional study. Methods Thirty-four patients with diplopia (median age 63, range 14-84 years) completed the Adult Strabismus-20 questionnaire (100-0, best to worst HRQOL) and a diplopia questionnaire in a clinical practice before prism and in prism correction. Before prism, diplopia was “sometimes” or worse for reading and/or straight-ahead distance. Prism treatment success was defined as diplopia rated “never” or “rarely” on the diplopia questionnaire for reading and straight-ahead distance. Failure was defined as worsening or no change in diplopia. For both successes and failures, mean Adult Strabismus-20 scores were compared before prism and in prism correction. Each of the 4 Adult Strabismus-20 domains (self-perception, interactions, reading function, and general function) was analyzed separately. Results Twenty-three of 34 (68%) were successes and 11 (32%) were failures. For successes, reading function improved from 57 ± 27 (SD) before prism to 69 ± 27 in-prism correction (difference 12 ± 20, 95% CI 3.2-20.8, P = .02) and general function improved from 66 ± 25 to 80 ± 18 (difference 14 ± 22, 95% CI 5.0-23.6, P = .003). Self-perception and interaction domains remained unchanged (P > .2). For failures there was no significant change in Adult Strabismus-20 score on any domain (P > .4). Conclusions Successful correction of diplopia with prism is associated with improvement in strabismus-specific HRQOL, specifically reading function and general function.