Prevention of musculoskeletal disorders is supported by use of slanted rather than horizontal pointing devices, but user acceptance of the former may be compromised due to lower perceived ease of use. This study compares subjectively rated usability (N = 37) for three sizes of slanted computer mice and includes a horizontal small conventional device as a reference. For a random subset of the sample (n = 10), objective usability parameters were also elicited. Participants followed a standard protocol which is based on executing graphical pointing, steering, and dragging tasks generated by a purpose-built software. Subjective ratings were collected for each of the four pointing devices tested. The three slanted devices differed in size but were chosen because of an approximately similar slant angle (around 50–60 degrees relative to the horizontal plane). Additionally, effectiveness and efficiency were objectively calculated based on data recorded for the graphical tasks’ software for a random subset of the participants (n = 10). The results unveil small differences in preference in some of the subjective usability parameters across hand size groups. This notwithstanding, the objective efficiency results are aligned with the subjective results, indicating consistency with the hypothesis that smaller slanted devices relative to the user’s hand size are easier to use than larger ones. Mean values of weighted efficiency recorded in the study range from 68% to 75%, with differences across devices coherent with preference rank orders.