OBJECTIVES: Depression is more common among patients with arthritis than in general populations and it independently and synergistically affects the functional well-being and health-related quality of life (HRQoL).There is paucity of studies evaluating the effect of depression treatment on the HRQoL in individuals with co-existing arthritis and depression in real world settings.The aim of this study is to examine the association between depression treatment and HRQoL among adults with depression and arthritis.  METHODS: This retrospective longitudinal study was conducted using the 2009-2013 Medical Expenditure Panel Survey. The study sample consisted of adults (≥ 21 years), with co-existing depression and arthritis (N = 1692). HRQoL was assessed in the baseline and follow-up years. Depression treatment (only antidepressants, psychotherapy with or without antidepressants and neither antidepressants nor psychotherapy (no treatment)) was used as the main independent variable. Ordinary Least Square (OLS) regression models were built to examine the association between depression treatment categories and the HRQoL scores after controlling for the biological, psychological and socio-economic factors.  RESULTS: A majority of individuals reported taking only antidepressants, 23% reported receiving psychotherapy with or without antidepressants and 21% did not receive any depression treatment. Individuals who reported using only antidepressants or psychotherapy with or without antidepressants had lower follow-up mean [SE] PCS scores (38.13[0.54] and 39.76 [0.78] respectively) as compared to those without depression treatment (40.44[0.78]). Adjusted analyses showed no significant association between PCS scores and depression treatment. The mean [SE] follow-up MCS scores were higher for individuals taking only antidepressants as compared to those reporting no depression treatment (42.71[0.58] vs 40.79[0.78]). Adjusted analysis revealed that those with psychotherapy had lower MCS scores compared to those without depression treatment (beta= -1.51,P=0.009).  CONCLUSIONS: RCTs have shown improved HRQoL in individuals with co-existing arthritis and depression who are treated for depression.  However, such findings are not replicated in real world settings.