Improving HRQOL is the desired outcome for patients with stroke undergoing inpatient rehabilitation services. This study aimed to comprehensively identify the potential health-related quality of life (HRQOL) predictors in patients with stroke undergoing inpatient rehabilitation within the first year after stroke; thus far, such an investigation has not been conducted. We enrolled 119 patients (88 males, 31 females) with stroke, and examined 12 potential predictors: age, sex, stroke type, stroke side, duration after onset, cognition (Mini-Mental State Examination; MMSE), depression (Beck Depression Inventory-II), stroke severity (National Institutes of Health Stroke Scale; NIHSS), upper- and lower-extremity motor function scores of the Fugl–Meyer Assessment (FMA) scale, balance (Berg Balance Scale; BBS), and functional status (Functional Independence Measure). HRQOL was measured using Stroke Impact Scale (SIS) 3.0. NIHSS score predicted the strength domain and total SIS score (41.5 % and 41.7 % of the variances, respectively). BBS score was a major predictor of mobility and participation/role domains (48.6 % and 10 % of the variances, respectively). MMSE score predicted the memory and communication domains (22.5 % and 36.3 % of the variances, respectively). Upper extremity score of the FMA scale predicted the daily living/instrumental activities of daily life and hand function domains (40.3 % and 20.6 % of the variances, respectively). Stroke side predicted the emotion domain (11.6 % of the variance). NIHSS, MMSE, BBS, FMA, and stroke side predicted most HRQOL domains. These findings suggest that different factors predicted various HRQOL domains in patients with stroke.