Background Little is known about pain and opiate use at home directly after total knee replacement (TKR). Due to adverse effects, low opiate use is desired. An electronic health app (PainCoach) was developed to guide patients in pain control and opiate use. Objective The aim of this paper was to investigate the effects of the PainCoach app on pain control and opiate use in patients who underwent TKR during the first 2 weeks at home after surgery. Methods In an unblinded randomized controlled trial, patients scheduled for TKR were offline recruited and randomized to a PainCoach group or control group. In the PainCoach group, the PainCoach app was downloaded on each patient’s smartphone or tablet. In response to the patient’s input of the pain experienced, the PainCoach app gave advice on pain medication use, exercises/rest, and when to call the clinic. This advice was the same as that received during usual care. The control group received usual care. The primary outcomes were opiate use and visual analog scale (VAS) pain scores at rest, during activity, and at night during the first 2 weeks at home after surgery, which were collected daily from day 1 until 14 postoperatively by online questionnaires. The actual amount of app use was recorded, and active use was defined as ≥12 total app uses. Results The pain scores did not differ between the groups. The PainCoach group (n=38) used 23.2% less opiates (95% CI −38.3 to −4.4; P=.02) and 14.6% more acetaminophen (95% CI 8.2-21.3; P<.001) when compared with the findings in the control group (n=33). The PainCoach app was used 12 (IQR 4.5-22.0) times per patient. In the active PainCoach subgroup (n=19), the following were noted when compared with the findings in the control group: 4.1 times faster reduction of the VAS pain score during activity (95% CI −7.5 to −0.8; P=.02), 6.3 times faster reduction of the VAS pain score at night (95% CI −10.1 to −2.6; P=.001), 44.3% less opiate use (95% CI −59.4 to −23.5; P<.001), 76.3% less gabapentin use (95% CI −86.0 to −59.8; P<.001), and 21.0% more acetaminophen use (95% CI 12.6-30.0; P<.001). Conclusions The use of the PainCoach app contributes to reduced opiate use in the initial period at home after TKR. Active use of this app leads to a further reduction in opiate use and improved pain control. Trial Registration ClinicalTrials.gov NCT03961152; https://clinicaltrials.gov/ct2/show/NCT03961152